Microwave Assisted Oxidation of Benzyl Halides to Aldehydes and Ketones with 4-Hydroxypyridinium Nitrate Functionalized Silica Gel in Aqueous Media

Full text of DOI:10.1080/00304948.2021.1880838

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
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Microwave Assisted Oxidation of Benzyl Halides to
Aldehydes and Ketones with 4-Hydroxypyridinium
Nitrate Functionalized Silica Gel in Aqueous Media
Shermineh sadat Ghalehbandi, Dadkhoda Ghazanfari, Sayed Ali Ahmadi &
Enayatollah Sheikhhosseini
To cite this article: Shermineh sadat Ghalehbandi, Dadkhoda Ghazanfari, Sayed Ali Ahmadi &
Enayatollah Sheikhhosseini (2021) Microwave Assisted Oxidation of Benzyl Halides to Aldehydes
and Ketones with 4-Hydroxypyridinium Nitrate Functionalized Silica Gel in Aqueous Media, Organic
Preparations and Procedures International, 53:2, 176-183, DOI: 10.1080/00304948.2021.1880838
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
2021, VOL. 53, NO. 2, 176–183
https://doi.org/10.1080/00304948.2021.1880838
EXPERIMENTAL PAPER
Microwave Assisted Oxidation of Benzyl Halides
to Aldehydes and Ketones with 4-Hydroxypyridinium
Nitrate Functionalized Silica Gel in Aqueous Media
Shermineh sadat Ghalehbandi, Dadkhoda Ghazanfari, Sayed Ali Ahmadi, and
Enayatollah Sheikhhosseini
Department of Chemistry, Kerman Branch, Islamic Azad University, Kerman, Iran
ARTICLE HISTORY Received 5 February 2020; Accepted 24 August 2020
Aldehydes and ketones, available by numerous methods and from plentiful starting materials,
are vital classes of chemicals which serve as precursors and intermediates for the preparation
of such divergent products as drugs, vitamins and fragrances.1,2 One of the methods for the
synthesis of aldehydes and ketones is direct oxidation of organic halides.3,4 The oxidation of
benzyl halides into aldehydes is a well-known transformation in organic synthesis, although
the oxidation of aliphatic halides to aldehydes is not common and is more difficult than the
oxidation of benzyl halides.5,6 Up to now, several methods have been developed for direct
oxidation of halides to their corresponding carbonyl compounds. Dimethyl sulfoxide,7,8
N,N-dimethyl-4-nitrosoaniline,9 nitronate anion and Pd(PPh3),10 pyridine N-oxides,11 and
other amine oxides,12 chromate and dichromate systems,13 silver nitrate,14 pyrazinyl sulfox-
ides,15 Mg-Al hydrotalcite,16 V2O5,17 NaIO4-DMF,18 quinolinium chlorochromate,19 H5IO6 in
[C12mim][FeCl4],20 and amine oxides21–23 have been used in the conversion of alkyl halides
to aldehydes and ketones. Recently NaOH-modified graphitic carbon nitride
26
(g-C3N4),24 nano-Fe3O4@L-arginine-CD-Cu(II),25 (NH4)3[FeMo6O18(OH)6] with O2 and
amine-functionalized silica-coated iron-core nanoparticles27 have been reported for the prep-
aration of aldehydes and ketones from alkyl halides. However these procedures have some lim-
itations, such as long reaction times, low yields, high temperatures, being harmful to the
environment and difficult separation of the product from the reaction mixture. From an envir-
onmental and green chemistry viewpoint, there is a great need to develop new procedures
with a broad substrate scope that will address the above-mentioned drawbacks for the direct
oxidation of organic halides to their corresponding carbonyl compounds.
In this respect, leverage points for research concern the application of green oxidants,
green solvents, or solvent-free processes, development of new catalytic systems, and the
use of energy efficient heating methods. For example, microwave (MW) heating is one
of the simplest but most effective ways to enhance energy efficiency and productivity in
small-scale chemical production.28,29
Herein we wish to report the use of an eco-friendly heterogeneous oxidant based on
4-hydroxypyridinium nitrate functionalized silica gel for the oxidation of benzyl halides
to the corresponding carbonyl compounds. The oxidant is a stable solid and can be
CONTACT Dadkhoda Ghazanfari
ghazanfari@iauk.ac.ir
Department of Chemistry, Kerman Branch, Islamic Azad
University, Kerman, Iran
ß 2021 Taylor & Francis Group, LLC

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
177
Scheme 1. Preparation of oxidant.
Figure 1. FT IR spectra of a) 4-hydroxypyridine, b) SiO2 and c) 4-hydroxypyridine functionalized
silica gel.
prepared from the reaction of sodium 4-pyridinolate with an acidic activated silica gel
which is then reacted with HNO3 (Scheme 1).
4-Hydroxypyridine@SiO2 nanoparticles were synthesized (see Experimental section)
and then characterized. Figure 1 shows the FT-IR transmission spectra in the range of
4000–400 cmꢀ1 at room temperature. The sharp peaks at 873 and 1069 cmꢀ1 were
assigned to the Si–O-C stretching vibrations. This information was consistent with the
formation of 4-Hydroxypyridine@SiO2 nanoparticles.
The effect of microwave irradiation on the reaction times as well as the product
yields was first established by reference experiments, after which it was sought to limit
the amount of reagent in the mixture, and bring the reaction time under control.
Table 1 indicates the results obtained for reactions done on 10 mmole scale.

178
S. S. GHALEHBANDI ET AL.
Table 1. Optimization of conditions in the reaction of benzyl chloride with 4-hydroxypyridinium
nitrate functionalized silica gel under microwave irradiation in aqueous media.a
Entry
Substrate: Oxidantb
Total Irradiation Time (min)
MW Power (W)
Conversionc (%)
Yieldd (%)
1
2
3
4
5
6
7
8
1:3
1:2
stirred at reflux conditions for 4 h
–
66
100
100
100
95
61
98
98
98
91
91
98
98
93
93
50
63
5
4
3
3
4
3
4
4
6
400
400
400
300
300
400
400
400
400
600
600
1:1.5
1:1.2
1:1.2
1:1.1
1:1.1
1:1.1
1:1
1:1
1:1.1
1:1.1
95
100
100
96
96
57
9
10
11e
12f
40
20
69
aReaction conditions: benzyl chloride, oxidant and H2O (20 ml) under microwave irradiation.
bMolar ratio.
cDetermined by GC.
dIsolated product (bezaldehyde).
eWith 4-hydroxypyridinium nitrate in the absence of silica gel.
fWith 4-hydroxypyridinium nitrate functionalized silica gel in the absence of H2O.
The most desirable results (see Experimental section for full protocol) could be
achieved on a 10 mmol scale when the ratio of substrate to oxidant was 1:1.1, in 20 ml
of H2O at 400 W microwave irradiation in two sequences for a total of 3 minutes
(entry 7). In the presence of 4-hydroxypyridinium nitrate, instead of our new oxidant,
or in the absence of water, more extreme conditions were required (entries 11 and 12)
to achieve useful conversions to product. Our experiments indicated that reactive alco-
hols and amines such as benzyl alcohol and benzyl amine remained inert under these
reaction conditions.
We found that a number of substituted benzyl bromides and benzyl chlorides were
readily oxidized to the corresponding aldehydes and ketones in high yields in total
irradiation times of 3-6 minutes under similar conditions. There were no signs of fur-
ther oxidation of benzaldehydes to benzoic acids (Table 2, entries 1-12, 17-24). Prompt
oxidation of the secondary halides into the respective ketones was noted with significant
yields (entries 14, 25). Oxidation of cinnamyl chloride, was done to give cinnamalde-
hyde with high yields (entry 15). Alkyl halides remained inert under the conditions of
this reaction (entries 16, 26). The product aldehydes were not oxidized into the respect-
ive carboxylic acids, even when a higher mole ratio of the supported oxidant was used.
Extending the time did not lead to more reaction (entry 21).
Reusability of 4-hydroxypyridine functionalized silica gel was also investigated under
the optimized conditions. Quantitative retrieval of 4-hydroxypyridine functionalized sil-
ica gel was performed following every experiment through four cycles after hot filtra-
tion. Activation was done by treatment with concentrated HNO3. Following this, benzyl

Table 2. Oxidation of benzyl halides with 4-hydroxypyridinium nitrate functionalized silica gel under
microwave irradiation in aqueous media.
Entry
Substrate
Producta
Irradiation Time (min)
Isolated Yield (%)
1
2
3
4
5
6
7
8
R ¼ H
R ¼ p-OCH3
R ¼ o-OCH3
R ¼ m-OCH3
R ¼ o-Br
R ¼ H
R ¼ p-OCH3
R ¼ o-OCH3
R ¼ m-OCH3
R ¼ o-Br
3
3
3
3
3
4
5
5
5
3
3
3
5
98
100
98
98
91
93
87
87
88
97
98
98
96
R ¼ p-Br
R ¼ p-Br
R ¼ o-F
R ¼ o-F
R ¼ m-F
R ¼ m-F
9
R ¼ p-F
R ¼ p-F
10
11
12
13
R ¼ o-CH3
R ¼ p-CH3
R ¼ m-CH3
R ¼ o-CH3
R ¼ p-CH3
R ¼ m-CH3
14
5
98
15
16
5
87
CH3(CH2)6CH2Cl
–
10
NDb
17
18
19
20
21
22
23
24
25
R ¼ H
R ¼ H
3
4
3
3
6
3
4
4
5
99
96
96
100
100
89
90
97
100
R ¼ m-NO2
R ¼ p-NO2
R ¼ p-OCH3
R ¼ p-OCH3
R ¼ o-Br
R ¼ m-NO2
R ¼ p-NO2
R ¼ p-OCH3
R ¼ p-OCH3
R ¼ o-Br
R ¼ p-Br
R ¼ p-Br
R ¼ p-CH3
R ¼ p-CH3
26
CH3(CH2)4CH2Br
CH3(CH2)4CHO
10
NDb
aAll products were characterized by their physical and spectral data.31–33 Reactions monitored by TLC.
bNo product was detected.

180
S. S. GHALEHBANDI ET AL.
Table 3. Comparison of present method with some reported in the literature.
Entry
Substratea
Product
Reaction Conditions
Yield (%) Time Ref.
1
R ¼ NO2,
X ¼ Br
Benzyl bromide (5.85 mmol), Silver oxide
(2.93 mmol) and pyridine N-oxide (5.85 mmol) in
acetonitrile (10 mL) under nitrogen.
86 Over night 21
2
3
4
5
R ¼ H, X ¼ Br
R ¼ H, X ¼ Cl
Benzyl bromide (2 mmol), H2O2 (30%, 2 mL), ethanol 89
(15 mL), and reflux.
3 h
3.5 h
3 h
4
4
Alkyl chloride (2 mmol), H2O2 (30%, 2 mL), ethanol
83
(15 mL), and reflux.
Benzyl bromide (2 mmol), H2O2 (30%, 2 mL), ethanol 76
(15 mL), reflux
R ¼ CH3,
X ¼ Br
4
b
X ¼ Br, Cl
Benzyl halide (10 mmol), 4-hydroxypyridinium
nitrate functionalized silica gel (11 mmol) and
H2O (20 mL) and then NaOH (11 mmol) under
MW irradiation.
87-100 3-5 min
R ¼ H, CH3, OCH3, X, NO2
6
7
X ¼ Br
X ¼ Br
Reflux in 1:1 (v/v) acetonitrile/water mixture.
Benzyl bromide (5.85 mmol), Silver oxide
(2.93 mmol) and pyridine N-oxide
(5.85 mmol) in acetonitrile (10 mL)
under nitrogen.
Benzyl halide (10 mmol), 4-hydroxypyridinium
nitrate functionalized silica gel (11 mmol) and
H2O (20 mL) and then NaOH (11 mmol) under
MW irradiation.
85
1.8 h 30
82 Over night 21
b
8
X ¼ Br, Cl
98-100 3 min
aA number of positional isomers were investigated.
bPresent work.
chloride was oxidized and yields of 98, 95, 93, and 91% were obtained under our opti-
mized conditions. Tell-tale signals in the IR spectrum of the retrieved reagent were
observed at 873 and 1069 cmꢀ1 respective to Si-O-C stretching.
Comparison of the efficacy of 4-hydroxypyridinium nitrate @SiO2 for oxidation of
benzyl halides under microwave irradiation in aqueous media was performed with some
of those reported in the literature (Table 3).
In summary, 4-hydroxypyridinium nitrate functionalized silica is a reusable oxidant that
functions better than some previously reported reagents, with higher yields and shorter reac-
tion times, for the oxidation of benzyl halides to the corresponding carbonyl compounds
under microwave irradiation in aqueous media. It is our hope that this versatile and con-
venient reagent will find wider use among organic chemists requiring this oxidative process.
Experimental section
Chemicals were purchased from Merck, Aldrich, or Fluka and used without further
purification. Experiments were carried out in a closed vessel multi-mode Microsynth
Milestone laboratory microwave oven. The melting points were determined on an
Electrothermal 9100 apparatus. IR spectra were recorded on a Bruker Tensor 27

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
181
1
spectrometer. H NMR and 13C NMR spectra were recorded on a Bruker 250 MHz
spectrometer. For the data in Table 1, GC analysis of the reaction mixture was carried
out using an Agilent 7890A GC instrument coupled to a flame ionization detector.
Compounds were separated on a HP-5 capillary column (30 m, 0.25 mm, film thickness
0.25 lm). The column temperature was kept at 90 ꢁC for 3 min and programed to
230 ꢁC at a rate of 5 ꢁC/min. Injector and detector temperatures were 260 ꢁC and the
flow rate of helium as carrier gas was 1 mL/min. The reaction mixture in hexane was
directly injected into the GC injector under the above temperature program in order to
calculate the retention indices of substrate (benzyl chloride) and product. There were
no signs of further oxidation of benzaldehyde to benzoic acid. All products are well-
known compounds and they were identified by comparison of their physical and spec-
tral data with those in the literature cited.31–33 Representative original spectra data were
submitted for editorial review. All yields refer to pure isolated products.
General procedure for Preparation of 4-hydroxypyridine functionalized silica gel
(4-hydroxypyridine@SiO2)
A fresh solution of 1.9 g of 4-hydroxypyridine (20 mmol) in 20 ml of NaOH (0.1 N) was
added to 6 g silica gel (nano powder, 99þ%, 600 m2/g) and was stirred at ambient tem-
perature for 10 min; then it was activated by 12.8 ml of sulfuric acid (8.3 N); and the
mixture was stirred at 40 ꢁC, for 15 min until a milky solid was formed, which was col-
lected, washed with 50 ml water and dried at 60 ꢁC for 20 min.
General procedure for preparation of 4-hydroxypyridinium nitrate functionalized
silica gel (4-hydroxypyridinium nitrate@SiO2)
Concentrated HNO3 (1.25 mL) was added to a solution of 7.9 g 4-hydroxypyridinium
functionalized silica gel (containing 20 mmol 4-hydroxypyridine) in 40 ml of H2O within
2 min below 10 ꢁC, then the mixture was stirred at ambient temperature for 15 min until
a lemon-colored solid was formed. After filtration, the solid was dried at 90 ꢁC for 1 h.
The supported reagent could be kept for weeks in the dark without losing its activity.
This synthesized reagent (0.1 g) was titrated by a standard solution of NaOH (0.1 N) to
obtain its [Hþ] concentration which was 3.7 meq per gram of the powder.
General procedure for the oxidation of benzyl halides with 4-hydroxypyridinium
nitrate@SiO2 under microwave irradiation
A mixture of benzyl halide (10 mmol) and H2O (20 ml) was stirred, and then the mix-
ture was added to 4-hydroxypyridinium nitrate functionalized silica gel (2.46 g,
11 mmol) and stirred. The reaction was done at ambient temperature for half the time
indicated in Table 2 by microwave and then sodium hydroxide solution (0.440 g,
11 mmol, in 10 ml H2O) was added dropwise over a period of 5 min at room tempera-
ture with vigorous stirring. The mixture was irradiated again for the other half time
indicated in Table 2. The progress of the reaction was monitored by TLC (silica gel,
n-hexane: pet. ether (1:3) as eluent). When the reaction was complete, the reaction

182
S. S. GHALEHBANDI ET AL.
mixture was cooled and extracted with diethyl ether (3 ꢂ 20 ml), washed with cold
water, and dried over anhydrous sodium sulfate After filtration, the removal of solvent
gave a crude product which was passed through a short silica gel column with n-hexa-
ne:diethyl ether (1: 1) as solvent to afford the pure product. The retrieved regent (4-
hydroxypyridine@silica gel) was activated by treatment with 1.25 ml of concentrated
HNO3 to provide 4-hydroxypyridinium nitrate@SiO2, then reused for the oxidation.
Acknowledgments
We gratefully thank Islamic Azad University for its financial support to our research group.
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