Assessing the effectiveness of oxidative approaches for the synthesis of aldehydes and ketones from oxidation of iodomethyl group

Article abstract of DOI:10.1007/s11696-018-0657-6

Owing to excellent selectivity, high yield and stability towards over-reduction and over-oxidation, one of the impressive approaches to synthesize aldehydes and ketones is the oxidation of halomethyl groups. Numerous halomethyl oxidation-based methodologies to afford aldehydes and ketones are disclosed in the literature. Mostly, chloromethyl or bromomethyl group containing substrates have been used in the literature for performing oxidation. There are negligible data available in the literature that addresses the use of iodomethyl group containing substrates for transformation to aldehydes and ketones. In this research work, 110 reactions have been carried out to construct aldehydes and ketones from oxidation of iodomethyl group in benzylic iodides and allylic iodides using numerous well-known approaches reported in the literature. The classical approaches under observation include Sommelet oxidation, Kr?hnke oxidation, sodium periodate-mediated oxidative protocol, manganese dioxide-based oxidative approach, Kornblum oxidation and Hass–Bender oxidation. The eco-friendly approaches under observation include periodic acid-based IL protocol, periodic acid in vanadium pentoxide-mediated IL method, hydrogen peroxide in vanadium pentoxide-based approach and bismuth nitrate-promoted IL technique. In this investigation, yield, recyclability, cost-effectiveness, eco-friendliness and over-oxidation are the main parameters which are under observation. Among all these investigated techniques, periodic acid-based IL protocol, periodic acid in vanadium pentoxide-mediated IL method and hydrogen peroxide in vanadium pentoxide-based approach (aka. Chunbao oxidation protocol) were found to be highly efficient due to the following reasons: these approaches (1) provide excellent yields, (2) do not lead towards over-oxidation, (3) show good recyclability, (4) demonstrate high thermal stability and negligible flammability, and (5) require no special handling.

Full text of DOI:10.1007/s11696-018-0657-6

Chemical Papers
https://doi.org/10.1007/s11696-018-0657-6
ORIGINAL PAPER
Assessing the efectiveness of oxidative approaches for the synthesis
of aldehydes and ketones from oxidation of iodomethyl group
Muhammad Faisal1 · Sarwat Hussain1 · Azeem Haider1 · Aamer Saeed1 · Fayaz Ali Larik1
Received: 12 June 2018 / Accepted: 27 November 2018
© Institute of Chemistry, Slovak Academy of Sciences 2018
Abstract
Owing to excellent selectivity, high yield and stability towards over-reduction and over-oxidation, one of the impressive
approaches to synthesize aldehydes and ketones is the oxidation of halomethyl groups. Numerous halomethyl oxidation-
based methodologies to aford aldehydes and ketones are disclosed in the literature. Mostly, chloromethyl or bromomethyl
group containing substrates have been used in the literature for performing oxidation. There are negligible data available in
the literature that addresses the use of iodomethyl group containing substrates for transformation to aldehydes and ketones.
In this research work, 110 reactions have been carried out to construct aldehydes and ketones from oxidation of iodomethyl
group in benzylic iodides and allylic iodides using numerous well-known approaches reported in the literature. The classi-
cal approaches under observation include Sommelet oxidation, Kröhnke oxidation, sodium periodate-mediated oxidative
protocol, manganese dioxide-based oxidative approach, Kornblum oxidation and Hass–Bender oxidation. The eco-friendly
approaches under observation include periodic acid-based IL protocol, periodic acid in vanadium pentoxide-mediated IL
method, hydrogen peroxide in vanadium pentoxide-based approach and bismuth nitrate-promoted IL technique. In this
investigation, yield, recyclability, cost-efectiveness, eco-friendliness and over-oxidation are the main parameters which
are under observation. Among all these investigated techniques, periodic acid-based IL protocol, periodic acid in vanadium
pentoxide-mediated IL method and hydrogen peroxide in vanadium pentoxide-based approach (aka. Chunbao oxidation
protocol) were found to be highly efcient due to the following reasons: these approaches (1) provide excellent yields, (2)
do not lead towards over-oxidation, (3) show good recyclability, (4) demonstrate high thermal stability and negligible fam-
mability, and (5) require no special handling.
Keywords Aldehydes · Ketones · Sommelet · Kröhnke · Iodide · Iodomethyl
Introduction
methods used for the preparation of aldehydes and ketones
are oxidation of alkenes (Wang and Jiang 2010), alcohols
(Marko et al. 1996) and Wacker’s process (Backvall et al.
1979), etc. General methods for the preparation of aromatic
aldehydes are Gattermann–Koch reaction (Benington et al.
1954), the Reimer–Tiemann reaction (Wynberg and Mei-
jer 1982) and the Vilsmeier reaction (Marson 1992). For-
myl group can also be introduced from diferent precursors
such as a hydroxymethyl, a halomethyl, an acid chloride
or a methyl group present at aromatic nucleus. However,
the preparation of aldehydes and ketones from alkenes and
aryl alcohols is difcult due to over-oxidation of carboxylic
acids. The other methods have also drawbacks, for exam-
ple, some of them are rather aggressive, need comparatively
high or low temperature, provide unnecessary by-products
and involve acidic reaction conditions that restrict the selec-
tion of suitable substrate. Therefore, to avoid complications,
Aldehydes and ketones comprise a number of most versatile
and powerful building blocks that are available for various
synthetic transformations (Porcheddu et al. 2017; LoPachin
and Gavin 2014; Stellman 1998). The carbonyl group of
aldehydes and ketones is highly reactive and undergoes
a number of chemical conversions to form key industrial
products as well as intermediates for other molecules used
in important reactions of industrial preparations. Common
* Muhammad Faisal
mfaisal4646@gmail.com
* Aamer Saeed
aamersaeed@yahoo.com
1
Department of Chemistry, Quaid-I-Azam University,
Islamabad, Pakistan
Vol.:(0123456789)
1 3

Chemical Papers
many synthetic approaches have been developed in the lit-
erature. The most attractive route for the preparation of aro-
matic aldehydes and ketones is the oxidation of halome-
thyl groups on aromatic rings by diferent methods. This
approach is known to be very promising, because it requires
no special reaction conditions such as high pressure, tem-
perature and catalysts.
et al. 2003; Mukaiyama et al. 1981; Barbry and Champagne
1996). Therefore, the need of a convenient and mild reaction
procedure still stimulates a continuous research efort and
the introduction of new methods for the oxidation of aryl
halomethyls is still in demand.
Most of the researchers have been investigated only
chloromethyl or bromomethyl group on aromatic rings as
substrates for oxidation to carbonyl compounds. There are
negligible chemical reactions which address the use of iodo-
methyl group on aryl nucleus as a reactant for the prepara-
tion of aldehydes and ketones. Iodomethyl group containing
compounds are particularly interesting synthetic precursors
due to the fact that these precursors provide high yield in
short amount of time as compared to chloromethyl or bro-
momethyl group containing compounds. Their better leaving
group ability and high reactivity make them very promising
reagents, but these features frequently become a signifcant
drawback owing to slowly degradation of these compounds
during storage. On account of this, it would be suggested to
prepare iodomethyl containing compounds under reaction
conditions which enable further synthesis in the similar reac-
tion fask or use them immediately after preparation. Further,
in order to store iodide compounds for long period of time, it
is recommended to store iodides them in tetrafuoroethylene,
stainless steel or glass storage container and keep it over
silica gel in a dark vacuum desiccator at − 5 °C (Alvarez-
Manzaneda et al. 2005; Armarego et al. 2012; Palamone
et al. 2011).
The common approaches for conversion of halomethyls
to carbonyl compounds are Hass–Bender reaction (Hass and
Bender 1949), Sommelet reaction (Larock 1989), Krohnke
oxidation (Krohnke 1963) and Kornblum oxidation (Korn-
blum et al. 1959). Other methods for the preparation of
aldehydes from halomethyls involve oxidation of benzyl
chlorides or bromides by the action of MnO2 in chloroform
(Goswami et al. 2005), H5IO6 in ([C12mim][FeCl4]) (Hu
et al. 2010a, b), mercury-ethanolic alkali (McKillop and
Ford 1974), the Masaki photo-oxidation (Itoh et al. 2000),
H2O2/V2O5 and Aliquat 336 in boiling water (Li et al. 2003),
4-dimethylaminopyridine-N-oxide (Mukaiyama et al. 1981),
pyridine N-oxide under microwave irradiations (Barbry and
Champagne 1996), K2CrO4 in HMPA in the presence of a
crown ether (Cardilo et al. 1976), quinolinium chlorochro-
mate in an aqueous medium (Gupta et al. 2014), montmo-
rillonite K10–HIO3 (Barbry and Champagne 1996), NaIO4
(Das et al. 2003) and selenium compounds (Syper and Mlo-
chowski 1984). 30% H2O2 in ethanol by molybdate-based
heterogeneous magnetic catalyst has been used as an oxi-
dant in the oxidation of halomethyls to carbonyl compounds
(Bayat et al. 2105).
The basic aim of this research study is to investigate
the numerous protocols formerly available in the literature
for their efectiveness towards synthesis of aldehydes and
ketones through oxidation of iodomethyl group. In doing so,
we believe that the idea of using benzyl and alicyclic iodides
will be efective for the preparation of target carbonyl com-
pounds. Apart from these, important part of our research is
concerned with the development of eco-friendly reactions
that protect environment from hazards. Our research pre-
sents an efective, successful and eco-friendly work for the
preparation of aldehydes and ketones in high to excellent
yield by substituting the reported substrates with highly ef-
cient substrates. In this investigation, yield, recyclability,
cost-efectiveness, eco-friendliness and over-oxidation are
the main parameters which are under observation.
However, most of the above methods sufer from over-
oxidation, long reaction time, costly reagents, lower conver-
sions, difculties in work-up, environmental hazards, toxic
reagents, harsh reaction conditions, separation difculties
and specially exhibit no selectivity between the halides
except few reactions. Hass–Bender method is only satisfac-
tory for p-substituted benzylic substrates. Sommelet reac-
tion is limited to active halides such as benzyl/allyl halides
and α-halo-ketones (Hass and Bender 1949; Larock 1989;
Krohnke 1963; Kornblum et al. 1959; Goswami et al. 2005;
Hu et al. 2010a, b). Electron-defcient or ortho-substituted
rings are not efcient substrates for this reaction. Selenium
compounds are harmful to the environment, and the method
of amine N-oxide is not conveniently enough and sufers
with variable yields. The use of H2O2 is not satisfactory
for aliphatic bromides. Potassium nitrate-catalyzed proce-
dure still sufers from harsh reaction conditions. Oxidation
of the methyl group on the aromatic ring involves the use
of complicated equipments, catalysts and production of
side-products. Stoichiometric amounts of oxidants have
been used in most of these oxidations. The aliphatic halo-
methyls were less reactive with H5IO6/V2O5, the reactions
proceeded slowly and even under more drastic reaction con-
ditions, reactions are still uncompleted (Itoh et al. 2000; Li
Results and discussion
There are numerous popular approaches which are well
documented for the syntheses of aldehydes and ketones by
oxidation of bromomethyl or chloromethyl group. In this
research work, we have investigated these approaches for
their efciency towards construction of aldehyde and ketone
skeletons through oxidation of iodomethyl group. Eleven
1 3

Chemical Papers
benzyl and alicyclic iodides (reactants) were purchased for
this research work (Fig. 1). The results of the diferent inves-
tigations are summarized in Tables 1, 2, 3, 4, 5, 6, 7, 8, 9,
and 10.
17 produced the target compounds in better yield (71%),
while poor yield was given by substrate 15 (41%). The pos-
sible reason of greater reactivity of substrate 21 may be the
combined efect of resonance due to benzene ring and hyper-
conjugation due to methyl group present in the compound
which gives stability to the ionized form of the molecule
and increases the reactivity of molecule while the decreased
reactivity of substrate 21 may be due to the bulkiness created
in the molecule by the two benzene rings that hinders the
approach of HMTA to the molecule.
Oxidative transformation of iodomethyls
to carbonyl groups using Sommelet reaction
First of all, Sommelet reaction was selected for the prepara-
tion of aldehydes and ketones using library of iodomethyls
(Madathil et al. 2006). In this protocol, all the substrates
were treated with HMTA in the presence of 50% aqueous
acetic acidic at 100 °C for 2.4–4.5 h followed by reaction
with 1 M HCl at 100 °C. After carrying out a large num-
ber of reactions, we observed that all the substrates led to
the syntheses of aldehydes and ketones in reasonable yields
(41–71%). Benzaldehyde 2 was obtained from benzyl iodide
1 in 62% yield. Aldehyde 4 was produced from substrate 3
in 64% yield. Similarly, other iodides, i.e., 3, 4, 5, 6, 7, 8, 9,
10 and 11 led to target compounds in yields of 52, 41, 52,
44, 63, 63, 71, 54 and 54%, respectively. Substrates 21 and
Investigating Krohnke oxidation for aldehydes
and ketones synthesis from iodomethyls
The second approach applied for the production of alde-
hydes and ketones from all the substituted/non-substi-
tuted benzyl and alicyclic iodides was Krohnke oxidation
(Table 2) (Krohnke 1963). In this approach, the substrates
were frst vigorously stirred with excess pyridine at 100 °C
to furnish pyridinium salts. The salts were then converted
into nitrones by treatment with p-nitrosodimethylaniline in
Fig. 1 List of reactants and
products
1 3

Chemical Papers
Table 1 Synthesis of library of carbonyl compounds by iodomethyl oxidation through Sommelet reaction
Reactant
Product
1
3
5
7
9
11
12
3
2
4
6
8
10
Time (h)
3
2.5
64a
23
15
16
3.5
41a
NOB
3.2
52a
< 10
17
3.5
63a
12
19
20
3
3
Yield (%)c
62a
11
13
14
3
52a
< 10
21
54a
11
Acidic product yield (%)
Reactant
Product
18
22
Time (h)
4.5
71b
NOB
4
Yield (%)c
69a
23
44a
NOB
71a
NOB
Acidic product yield (%)
aReaction conditions: iodomethyl compound (0.05 mol), hexamethylene tetramine (0.09 mol), 25 mL of 50% acetic acid
bReaction conditions: iodomethyl compound (0.04 mol), hexamethylene tetramine (0.09 mol), 25 mL of 50% acetic acid
cYield of product after column chromatography; NOB not observed (no over-oxidation towards acidic product was observed)
Table 2 Synthesis of series of carbonyl compounds by iodomethyl oxidation through Krohnke reaction
Reactant
Product
1
3
5
7
9
11
12
10
74a
11
2
4
6
8
10
12
75a
5
Time (h)
10
82a
11
13
14
11
79a
> 12
12
81a
12
15
16
12
81a
NOB
11
12
67a
34
19
20
10
78a
NOB
Yield (%)c
78b
> 10
17
Acidic product yield (%)
Reactant
Product
21
22
12
80a
NOB
18
Time (h)
12
Yield (%)c
81a
NOB
Acidic product yield (%)
aReaction conditions: pyridinium salt (0.03 mol), p-nitrosodimethylaniline (0.06 mol)
bReaction conditions: pyridinium salt (0.08 mol), p-nitrosodimethylaniline (0.06 mol)
cYield of product after column chromatography; NOB=not observed (no over-oxidation towards acidic product was observed)
the presence of NaNH2 in water for 2.5–4.5 h at 20–30 °C
and then acid hydrolysis of nitrones aforded aldehydes or
ketones in 67–82% overall yield. This reaction produced
aldehydes and ketones in better yields as compared to
Sommelet oxidation. Benzyl iodides produced benzalde-
hydes in excellent yield, i.e., 82% while benzyl iodides
methylated at meta-positions yielded methylated benzal-
dehydes in moderate yield of 67%. Substrates 1, 3, 5, 7, 9,
11, 13, 15 and 20 produced aldehydes and ketones in yield
of 81, 78, 81, 67, 78, 74, 79, 81 and 79%, respectively, that
are also excellent from applications point of view.
1 3

Chemical Papers
Table 3 Synthesis of series of carbonyl compounds via sodium metaperiodate-based protocol
Reactant
Product
1
3
5
7
9
11
12
60
51a
44
2
4
6
8
10
Time (min)
60
51a
32
13
14
60
43a
33
60
120
25a
11
17
18
180
26c
NOB
120
41a
21
19
20
120
43a
NOB
60
Yield (%)d
43a
22
41a
> 20
21
Acidic product yield (%)
Reactant
Product
15
16
100
35b
NOB
22
Time (h)
120
49a
NOB
Yield (%)d
Acidic product yield (%)
aReaction conditions: iodomethyl compound (1 mmol), sodium metaperiodate (1 mmol)
bReaction conditions: iodomethyl compound (0.8 mmol), sodium metaperiodate (1 mmol)
cReaction conditions: iodomethyl compound (0.5 mmol), sodium metaperiodate (1 mmol)
dYield of product after column chromatography; NOB not observed (no over-oxidation towards acidic product was observed)
Table 4 Synthesis of series of carbonyl compounds via manganese dioxide-based protocol
Reactant
Product
1
3
5
7
9
10
5
11
12
6
2
4
6
8
Time (h)
4
6
7
5
Yield (%)c
62a
33
13
14
6
53a
11
15
16
7
22a
11
17
18
7
43a
32
19
20
4
42a
23
21
22
5
43a
29
Acidic product yield (%)
Reactant
Product
Time (h)
Yield (%)c
41a
35
30a
NOB
11b
NOB
51a
NOB
52a
NOB
Acidic product yield (%)
aReaction conditions: iodomethyl compound (3 mmol), activated manganese dioxide (15 mmol)
bReaction conditions: iodomethyl compound (2.5 mmol), activated manganese dioxide (15 mmol)
cYield of product after column chromatography; NOB=not observed (no over-oxidation towards acidic product was observed)
in the presence of DMF under the atmosphere of argon
at temperature of 150 °C for 60–180 min to aford alde-
hydes or ketones in 25–51% (Table 3) (Das et al. 2003).
This approach was less efective for the production of tar-
get carbonyl compounds in high yields from most of the
prepared iodomethyl groups present on diferent nucleus
Sodium metaperiodate‑based iodomethyls
oxidation to aldehydes and ketones
The third procedure applied to the production of target
carbonyl compounds was Sasmita reaction. In this proto-
col, reactants were treated with an oxidizing agent NaIO4
1 3

Chemical Papers
Table 5 Synthesis of series of carbonyl compounds via Kornblum oxidation
Reactant
Product
1
3
5
7
9
11
2
4
6
8
10
12
Time (h)
20
30
20
50
50
20
Yield (%)c
81a
NOB
13
83a
NOB
15
62b
Traces
17
82a
Traces
19
72a
NOB
21
61a
Traces
Acidic product yield (%)
Reactant
Product
14
16
18
20
22
Time (h)
30
40
50
20
40
Yield (%)c
79a
NOB
63a
NOB
83b
NOB
78a
NOB
71a
NOB
Acidic product yield (%)
aReaction conditions: iodomethyl compound (16 mmol), dimethyl sulfoxide (50 ml), NaHCO3 (84 mmol)
bReaction conditions: iodomethyl compound (16 mmol), dimethyl sulfoxide (70 ml), NaHCO3 (90 mmol)
cIsolated yield; NOB not observed (no over-oxidation towards acidic product was observed)
Table 6 Oxidation of series of iodomethyls by Hass–Bender reaction
Reactant
Product
1
3
5
7
9
10
4
11
12
4
2
4
6
8
Time (h)
4
5
4
4
Yield (%)c
78a
10
13
14
4
72a
5
52a
20
17
18
5
82a
10
19
20
4
69a
10
21
22
4
61a
20
Acidic product yield (%)
Reactant
Product
15
16
5
Time (h)
Yield (%)c
79a
10
49a
NOB
83b
NOB
75a
NOB
71a
Acidic product yield (%)
NOB
aReaction conditions: iodomethyl compound (2.67 mmol), 2-nitropropane (3.72 mmol), sodium methoxide (5.01 mmol)
bReaction conditions: iodomethyl compound (1 mmol), 2-nitropropane (3.72 mmol), sodium methoxide (5.01 mmol)
cYield of product after column chromatography; NOB=not observed (no over-oxidation towards acidic product was observed)
except benzyl and methylated benzyl iodide which pro-
duced aldehydes in good yield, i.e., 51%. Also, the same
reason as mentioned above may be addressed for substrate
1 while methyl group substituted at para position to iodo-
methyl group also enhances the reactivity therefore; these
compounds led to better yields. The remaining compounds
are not much compatible with this reaction that may be
due to the insolubility of these compounds in DMF, poor
reaction with NaIO4, unsuitable reaction temperature as
well as other unsuitable reaction conditions.
1 3

Chemical Papers
Table 7 Oxidation of iodomethyls by periodic acid in IL 1-dodecyl-3-methylimidazolium iron chloride
Reactant
Product
Time (h)
Yield (%)
Acidic product yield (%)
Reactant
Product
Time (h)
Yield (%)
1
3
5
7
9
11
2
4
6
8
10
12
3
4
3
3
4
3
91a,b
NOB
13
92a,b
NOB
15
81a,c
Traces
17
87a,b
NOB
19
78a,c
10
89a,b
NOB
21
14
16
18
20
22
3
3
4
5
5
92a,b
NOB
89a,b
NOB
82a,b
NOB
81a,b
NOB
89a,b
NOB
Acidic product yield (%)
aReaction conditions: iodomethyl compound (30 mmol), [C12mim][FeCl4] (1.2 mmol), H5IO6 (33 mmol)
bIsolated yield (no column purifcation required)
cIsolated yield after column chromatography; NOB not observed (no over-oxidation towards acidic product was observed)
Table 8 Oxidation of iodomethyls by periodic acid and vanadium pentoxide in 1-butyl-3-methylimidazolium hexafuorophosphate
Reactant
Product
Time (h)
Yield (%)
Acidic product yield (%)
Reactant
Product
Time (h)
Yield (%)
1
3
5
7
9
11
2
4
6
8
10
4
12
5
6
7
4
4
92a,b
NOB
13
92a,b
NOB
15
87a,c
Traces
17
91a,b
NOB
19
83a,c
5
89a,b
NOB
21
22
7
14
16
18
20
5
7
9
4
83a,b
NOB
84a,b
NOB
85a,b
NOB
91a,b
NOB
94a,b
NOB
Acidic product yield (%)
aReaction conditions: iodomethyl compound (30 mmol), [bmpy]PF6 (15 mL), H5IO6 (36 mmol), V2O5 (0.9 mmol)
bIsolated yield (no column purifcation required)
cIsolated yield after column chromatography; NOB=not observed (no over-oxidation towards acidic product was observed)
deliver carbonyl compounds in 11–62% yield (Table 4).
Studies confirmed that this reaction was not effective
in case of benzyl iodides as the yields of aldehydes and
ketones were very poor by using some substrates such
as 5, 7, 9, 13, 15, 11, and 17. However, the remaining
Transformation of iodomethyls to aldehydes
and ketones using manganese dioxide
The fourth approach employed in this research work was
Goswami approach (Goswami et al. 2005). In this reac-
tion, all the iodomethyls were reacted with an oxidiz-
ing agent MnO2 in chloroform under reflux for 4–7 h to
1 3

Chemical Papers
Table 9 Synthesis of series of carbonyl compounds via Chunbao oxidation protocol
Reactant
Product
Time (h)
Yield (%)
Acidic product yield (%)
Reactant
Product
Time (h)
Yield (%)
1
3
5
7
9
11
2
4
6
8
10
12
6
8
8
10
7
6
86a,d
NOB
13
82a,d
NOB
15
89b,e
Traces
17
81b,d
NOB
19
82a,d
NOB
21
92a,d
NOB
14
16
18
20
22
6
6
8
8
6
86a,d
NOB
81a,d
NOB
90c,d
NOB
84a,d
NOB
89a,d
NOB
Acidic product yield (%)
aReaction conditions: iodomethyl compound (3 mmol), H2O (30 mL), H2O2 (30%, 18 mmol), V2O5 (0.06 mmol), Aliquat 336 (0.6 mmol)
bReaction conditions: iodomethyl compound (2.5 mmol), H2O (30 mL), H2O2 (30%, 18 mmol), V2O5 (0.06 mmol), Aliquat 336 (0.6 mmol)
cReaction conditions: iodomethyl compound (2 mmol), H2O (30 mL), H2O2 (30%, 18 mmol), V2O5 (0.06 mmol), Aliquat 336 (0.6 mmol)
dIsolated yield (no column purifcation required)
eIsolated yield after column chromatography; NOB not observed (no over-oxidation towards acidic product was observed)
Table 10 Synthesis of series of carbonyl compounds via Khodaei oxidation method
Reactant
Product
Time (h)
Yield (%)
Acidic product yield (%)
Reactant
Product
Time (h)
Yield (%)
1
3
5
7
9
11
2
4
6
8
10
12
1
2
1
1
1.5
1.5
87a,e
< 5
89a,e
< 5
13
87a,e
< 5
15
81a,e
< 10
17
81a,e
< 10
19
78a,e
Traces
21
14
1
16
18
20
22
1.6
79b,d
NOB
2
1
1.5
89a,e
Traces
83c,d
NOB
81a,d
NOB
85a,d
NOB
Acidic product yield (%)
aReaction conditions: iodomethyl compound (3 mmol), TBAF (1.5 mmol), Bi(NO3)3·5H2O (3.3 mmol)
bReaction conditions: iodomethyl compound (2.5 mmol), TBAF (1.5 mmol), Bi(NO3)3·5H2O (3.3 mmol)
cReaction conditions: iodomethyl compound (2 mmol), TBAF (1.5 mmol), Bi(NO3)3·5H2O (3.3 mmol)
dIsolated yield (no column purifcation required)
eIsolated yield after column chromatography; NOB not observed (no over-oxidation towards acidic product was observed)
substrates produced target carbonyl compounds in
moderate yields. The better yields of aldehydes were
obtained using simple benzyl iodide under Goswami pro-
tocol which was 62%.
1 3

Chemical Papers
1-dodecyl-3-methylimidazolium iron chloride [C12mim]
[FeCl4] at temperature of 50 °C for 3–5 h. This approach
provided 78–92% yield in short reaction time (Table 7).
Ionic liquids (ILs) have gradually gained broad apprecia-
tion as eco-friendly solvents due to their excellent properties,
for example, non-volatility and non-fammability at room
temperature, high thermal stability, wide electrochemical
window, large liquid range, and strong capability to solubi-
lize a lot of compounds (Rogers and Seddon 2005). Studies
demonstrated that IL-based approach is admirable procedure
for the oxidation of both substituted/non-substituted benzyl
iodides and alicyclic iodides with excellent yields along with
good catalytic recyclability. Benzyl iodide, 1-(iodomethyl)-
naphthalene and 4-methoxybenzyl iodide produced alde-
hydes and ketones with excellent yields of 91% and 92%,
respectively. The remaining substrates were also efcient
in transforming to targeted carbonyl compounds with better
yields as shown in Table 2.
Efectiveness of Kornblum oxidation to construct
carbonyl entities from iodomethyls oxidation
The ffth protocol for the preparation of targeted carbonyl
compounds used in this research work was Kornblum oxi-
dation (Kornblum et al. 1959). All the eleven substrates
were heated for 20–50 min at temperature of 150°C under
nitrogen atmosphere in the presence of DMSO using a base
NaHCO3. This reaction was a best experience for the syn-
thesis of aldehydes and ketones. All the substituted/non-
substituted benzyl and alicyclic iodides produced the target
carbonyl compounds in good to excellent yields (61–83%)
and in short reaction time (Table 5). Substrates 3 and 17
were observed to be more efcient substrate in converting
into aldehyde and ketone using this procedure with excel-
lent yield of 83%. Only methylated benzyl iodides produced
aldehydes in moderate yield, i.e., 61%. All the remaining
substrates also produced better to excellent yield of targeted
carbonyl compounds. The possible reason of this may be
the better solubility of all these compounds in DMSO and
favorable reaction conditions for all substituted benzyl and
alicyclic iodides.
Recyclability of ionic liquid and the catalyst
The recyclability of the ionic liquid and catalyst was also
studied using (iodomethyl)benzene 1 as substrate under
identical reaction conditions. Upon reaction completion, the
product (benzaldehyde 2) was extracted with dichlorometh-
ane from reaction mixture and the rest of the ionic liquid
and the catalyst were recovered by decantation of aqueous
hydrogen halide produced in the reaction and concentrated
under vacuum. (Iodomethyl)benzene 1 was then recharged to
the recovered catalyst system and then rerun under identical
reaction conditions. The results indicated that the catalyst
could be recycled for almost six times with only a small
loss of activity. Briefy, the fresh ionic liquid and catalyst
aforded compound 2 in 91% yield in reaction time of 3 h. In
the frst run, the ionic liquid and catalyst provided compound
2 in 86% yield in the same period of reaction time. In the
second run, the ionic liquid and catalyst delivered compound
2 in 85% yield in reaction time of 3.5 h. In the third and
fourth run, the ionic liquid and catalyst generated compound
2 in 80% yield in reaction time of 4 h. The next run furnished
compound 2 in 71% yield in reaction time of 4.3 h. Hence,
the approach was highly operative and recyclable catalyst
for the preparation of carbonyl compounds.
Hass–Bender reaction for the production
of carbonyl units from iodomethyls
Hass–Bender oxidation was the sixth procedure performed
for converting iodomethyl groups of diferent benzyl and ali-
cyclic nucleus into aldehydes and ketones (Hass and Bender
1949). All substrates were treated with 2-nitropropane in
the presence of NaOEt in 2-propanol at room temperature
for 4–5 h to obtain carbonyl compounds in 49–83% yield
(Table 6). The reaction mixture was heated under refux.
Studies showed that this method is convenient and efcient
for the oxidation of all nucleus having iodomethyl groups
into targeted compounds in better and moderate yield. Excel-
lent yield was obtained from oxidation of benzyl iodide
while diphenyl-methyl iodide substrate gave moderate yield
(Faisal et al. 2018). The remaining substituted/non-substi-
tuted benzyl and alicyclic iodides also gave better results
with this reaction by producing these compounds in better
yield. The reaction showed that these iodides can act as bet-
ter substrates under reaction conditions used in Hass–Bender
reaction.
Oxidation with periodic acid and vanadium
pentoxide in 1‑butyl‑3‑methylimidazolium
hexafuorophosphate
Oxidation with periodic acid in IL
1‑dodecyl‑3‑methylimidazolium iron chloride
The next method used for mild oxidation of alicylic and
aromatic methyl iodides was also reported to be highly
efective and environment friendly (Hu et al. 2010a, b).
In this approach, all the iodomethyls were treated with
H5IO6 in the presence of V2O5 as a catalyst and ionic
The next method used in the research work for oxidation of
tabulated substrates was reported to be highly efective and
environment friendly (Hu et al. 2010a, b). In this method,
iodomethyls were treated with periodic acid (H5IO6)
as an oxidizing agent in the presence of an ionic liquid,
1 3

Chemical Papers
liquid 1-butyl-3-methylimidazolium hexafuorophosphorate
([bmpy][PF6]) as a solvent at 70 °C for 4–9 h to deliver car-
bonyl compounds in excellent yields (83–94%). This method
was also very potent and convenient for the production of
carbonyl compounds by oxidation of all selected substrates
(Table 8). 3,4-Dimethylbenzyl iodide, benzyl iodide and
1-(iodomethyl)-naphthalene were the most reactive for con-
verting into aldehydes and ketones by this procedure with
maximum yields of 94% and 92%, respectively, while all the
remaining iodides were also very efcient in transforming to
carbonyl compounds with excellent yields.
halomethyl group. Under reaction conditions, nucleophile
VO(O2)−2 is formed. In the next step, halo group is directly
attacked by nucleophile VO(O2)−2 to furnish an intermedi-
ate ArCH2OV(O2)2. After losing a proton, intermediate
ArCH2OV(O2)2 decomposes into carbonyl compound (Li
et al. 2003). To investigate the yield sustainability on large-
scale reaction, some reactions were performed with 30, 60
and 90 mmol of iodomethyl compounds. The investigation
revealed that the yields of Table 9 remained sustainable on
a large scale.
Recyclability of the catalyst
Recyclability of ionic liquid and the catalyst
The recyclability of this synthetic approach was also studied
using (iodomethyl)benzene 1 as substrate under identical
reaction conditions. Upon reaction completion, the oily layer
was separated from reaction mixture and aqueous phase
was reused under identical reaction conditions. The results
indicated that the catalyst could be recycled for almost four
times with only a small loss of activity. Briefy, the fresh
catalyst aforded 2 in 86% yield in reaction time of 6 h. 80,
78, 77 and 65% yields of 2 over the reaction time of 6–8 h
for the frst, second, third and fourth run, respectively.
The recyclability of the ionic liquid and catalyst was also
studied using (iodomethyl)benzene 1 as substrate under
identical reaction conditions. Upon reaction completion, the
product (benzaldehyde 2) was extracted with dichlorometh-
ane from reaction mixture and the rest of the ionic liquid
and the catalyst were recovered by decantation of aqueous
hydrogen halide produced in the reaction and concentrated
under vacuum. (Iodomethyl)benzene 1 was then recharged to
the recovered catalyst system and then rerun under identical
reaction conditions. Results indicated that the catalyst could
be recycled for almost six times with only a small loss of
activity. Briefy, the fresh ionic liquid and catalyst aforded
compound 2 in 92% yield in reaction time of 5 h. In frst
cycle, the ionic liquid and catalyst provided compound 2 in
82% yield in reaction time of 6 h. In second and third cycle,
the ionic liquid and catalyst delivered compound 2 in 81%
and 80% yield, respectively, in reaction time of almost 6 h.
Fourth and ffth cycle generated compound 2 in yields of
75% and 65%, respectively, in the reaction time of almost
7 h. Hence, the approach was observed to be highly opera-
tive and recyclable catalyst for the preparation of carbonyl
compounds.
Bismuth(III) nitrate pentahydrate
in tetrabutylammonium fuoride for in situ
oxidation of iodomethyl
The last method that we used for the conversion of alicyclic
and aromatic iodides to carbonyl compounds was Khodaei
method (Khodaei et al. 2005). This is actually the controlled
oxidation of alkyl or aryl halomethyls without further oxida-
tion to carboxylic acid and reaction stops at aldehydes and
ketones. All the alicylic and aromatic iodides were treated
with bismuth nitrate pentahydrate Bi(NO3)3·5H2O in the
presence of tetrabutylammonium fuoride (TBAF) as an
in situ oxidant at 100°C. In short reaction period of 1–2 h,
all the iodomethyls were transformed into the products in
yield of 78–89% (Table 10). All the iodomethyls produced
the targeted compounds in better yields except benzyl iodide
and 4-methoxybenzyl iodide that were oxidized efciently
than other with excellent yield of 89%. One of the merits
of bismuth nitrate pentahydrate is that it can be used with
large variety of alkyl halomethyls and does not need the
isolations of intermediate aldehydes. It has been experimen-
tally verifed by Khodaei et al. that there is no formation
of alcoholic product (by solvolysis) during the oxidation of
halomethyl group (Khodaei et al. 2005). To investigate the
yield sustainability on large-scale reaction, some reactions
were performed with 30, 60 and 90 mmol of iodomethyl
compounds. The investigation revealed that the yields of
Table 10 remained sustainable on a large scale.
Iodomethyl oxidation via hydrogen peroxide
catalyzed by V2O5 and Aliquat 336
Chunbao protocol was the ninth method which was applied
for the oxidation of iodomethyl groups to aldehydes and
ketones. In this reaction, all the iodomethyls were treated
with H2O2/V2O5 in boiling water with Aliquat 336 as phase
transfer catalyst (Li et al. 2003). This approach provided
excellent yields (81–92%) in all cases. The reaction was very
efcient in converting all the iodides (in better yield) into
aldehydes and ketones (Table 9). The excellent yield was
obtained by oxidation of 1-(iodomethyl)-4-methylbenzene
11 (92%) while all the remaining compounds showed bet-
ter oxidation potential with high yields. It has been experi-
mentally verifed by Li et al. that there is no formation of
alcoholic product (by solvolysis) during the oxidation of
1 3

Chemical Papers
Table 11 Scope of diferent transformational approaches towards oxidation of 1, 23 and 24
Methodology name
Time
Yield (%)a
Yield (%)b
Yield (%)c
Sommelet reaction
Krohnke oxidation
NaIO4-based oxidation
MnO2-mediated approach
Kornblum oxidation
3 h for 1
10 h for 1
1 h for 1, 40 min for 23
4 h for 1, 2 h for 23, 6 h for 24
20 h for 1, 10 h for 23
4 h for 1, 3 h for 23, 4 h for 24
3 h for 1, 2 h for 24
5 h for 1, 3 h for 24
6 h for 1, 14 h for 23, 6 h for 24
1 h for 1, 1 h for 23, 1.5 h for 24
62
82
51
62
81
78
91
92
86
89
NF
NF
80
80
80
NF
NF
NF
40
NF
79
94
92
70
90
Hass–Bender reaction
72
H5IO6 in IL-based oxidation
H5IO6 and V2O5 in IL-based oxidation
Chunbao oxidation protocol
Khodaei oxidation method
NF
NF
84
91
NF not found in literature
aIsolated yield of product of oxidation of (iodomethyl)benzene 1
bIsolated yield of product of oxidation of (bromomethyl)benzene 23
cIsolated yield of product of oxidation of (chloromethyl)benzene 24
With all these results from experiments in hands, it is
clear that diverse kind of both substituted/non-substituted
benzylic and alicyclic iodides, both primary and secondary,
could be efectively oxidized to the corresponding aldehydes
and ketones in poor to excellent yield efectively. Diferent
functional groups, for example, methyl, methoxy and alkene
double bonds can stand with reaction conditions used in these
reactions. It can also be considered that the presence of these
substituents on the aromatic nucleus may have some efect on
the rate of oxidation reaction. The position of the substituents
on benzene ring may also afect the oxidizing property of
these molecules, for instance, substituents present at ortho
and para positions increase the reactivity of substrates while
at meta-positions deactivate the aromatic ring towards further
reaction. In some cases, substituents increase the reactivity
while in other cases; they decrease the reactivity towards oxi-
dation which may be due to the substituent efect along with
replacing the substituents such as chlorine and bromine on
the aromatic and alicyclic rings with iodine.
Research reveals that, overall, oxidation of iodomethyl groups
provides comparable yield in less amount of time as compared
to oxidation of chloromethyl or bromomethyl groups. The
results also show that green approaches are superior over clas-
sic approaches. Among all the techniques, periodic acid-based
IL protocol, periodic acid in vanadium pentoxide-mediated IL
method and hydrogen peroxide in vanadium pentoxide-based
approach (aka. Chunbao oxidation protocol) were found to be
highly efcient due to the following reasons: these protocols
(1) provide excellent yields (>80%) in most cases, (2) do not
lead towards over-oxidation, (3) are highly recyclable without
any important loss of catalytic efciency, (4) have excellent
capacity to dissolve many chemicals, (5) show negligible
fammability and large thermal stability, (6) are inexpensive,
(7) are eco-friendly, and (8) require no special handling (easy
work-up). Iodomethyl groups ofer a very simple, mild, ef-
cient and inexpensive means to substituted aldehydes and
ketones. This work would be applicable for large-scale syn-
thesis of various carbonyl compounds and could be helpful for
designing many organic reactions on industrial scale. Moreo-
ver, advantages of this research work include such catalytic
systems and ionic liquids which are easy to handle and very
much recyclable without signifcant loss of catalytic activity.
Most of the catalysts such as V2O5 and Aliquat 336 are found
to be economical, efcient and stable under diferent reactions
conditions.
Table 11 is based on the comparison of yields of benza-
ldehyde 2 obtained from oxidation of (iodomethyl)benzene
1, (bromomethyl)benzene 23 and (chloromethyl)benzene 24
via applying diferent transformational approaches. The aim
of the Table 11 is to disclose the relative capability of difer-
ent oxidation protocols towards oxidation of organic halides
to aldehydes and ketones.
Conclusion
Experimental
We have investigated various classical and eco-friendly meth-
ods reported in the literature for production of aldehydes and
ketones by modifying the substrates from chloromethyl and
bromomethyl groups to a more reactive iodomethyl group.
Materials and general methods
Chemicals, reagents and solvents were obtained from Spec-
trochem, SRL, Merck, Aldrich and Process Chemicals. The
1 3

Chemical Papers
routine reaction monitoring was carried out with pre-coated
silica gel-60 TLC plates (Aldrich, Silica gel H TLC Grade).
Chromatographic purifcation was performed with silica gel
(70–230 mesh; Wakogel® C-100E). The column size was
19×200 mm. Melting points were measured with a capillary
Reaction content was shaken for about 15 min and extracted
with 50 ml portions of ether for three times. The combined
ether extract was washed with water and dried over Na2SO4.
Ether was evaporated and the obtained residue was puri-
fed by column chromatography using hexane:ethyl acetate
(20 mL:80 mL) to provide carbonyl compound (67–82%).
1
apparatus. H NMR was evaluated on a Varian Gem2300
300 MHz spectrometer (chemical shifts are w.r.t residual
solvent peaks; tetramethylsilane= δ 0 ppm). All coupling
constants are expressed in Hz and are absolute values.
General procedure for sodium metaperiodate‑based
oxidation
Iodomethyl compound (1 mmol) and sodium metaperio-
date (NaIO4) (0.21 g, 1 mmol) were taken in round bottom
vessel. 15 ml of DMF was added to reaction vessel to dis-
solve the mixture. The reaction content was refuxed and the
reaction progress was examined by TLC using 10% ethyl
acetate in hexane solvent system. Reaction was completed
in 60–180 min. After reaction completion, reaction mixture
was cooled and 20 ml of water was added to reaction con-
tent. Then, extraction was performed in ether (2× 30 ml).
The ether layer was isolated and was dried over anhydrous
magnesium sulfate and fltered. Solvent was evaporated and
crude product was purifed by column chromatography on
silica gel using 10% ethyl acetate in hexane as mobile phase.
The 25–51% of carbonyl compound was obtained.
General procedure for Sommelet reaction
The mixture of 25 mL of 50% acetic acid, 0.05 mol of iodo-
methyl substrate and 12.66 g (0.09 mol) of hexamethylenetet-
ramine was taken in round bottom fask. The reaction content
was refuxed with continuous stirring for appropriate period
of time [TLC control (EtOAc/n-hexane 1:9); 2.5–4.5 h] at
100 °C. After that 10 mL of 1 M HCl was poured in reaction
mixture and stirring was maintained for additional 15 min at
same temperature. Then, the reaction mixture was cooled to
r.t. Organic layer was washed with DCM, dried over anhy-
drous MgSO4 and concentrated in vacuo to give a crude liq-
uid product. Crude liquid product was purifed by column
chromatography using hexane–ethyl acetate (20:80) as an
eluent to provide carbonyl compound (41–71%).
General procedure for manganese
dioxide‑mediated approach
General procedure for Krohnke oxidation
A mixture of iodomethyl compound (3 mmol) and acti-
vated manganese dioxide (1.44 g, 15 mmol) in chloroform
(30 mL) was refuxed for 4–7 h at 60 °C. TLC in petroleum
ether–dichloromethane (3:1) was employed to monitor reac-
tion progress. After reaction completion, which was indi-
cated by TLC, the reaction mixture was fltered and washed
with CHCl3. The combined fltrates after evaporation and
purifcation with silica gel (10% ethyl acetate in hexane)
aforded carbonyl compound (11–62%).
Preparation of pyridinium salt
Pyridinium salt was obtained in a quantitative yield from
iodomethyl substrate (0.02 mol) by stirring with excess pyri-
dine (50 ml) at 100 °C for 3 h.
Preparation of the nitrone
A suspension of 0.03 mol of pyridinium salt and 3 g of sodium
amide was prepared in 60 ml pyridine. 9 g (0.06 mol) of highly
purifed p-nitrosodimethylaniline and 15 ml of water were
added to the suspension with stirring while maintaining the
reaction temperature to about 20–30 °C. The reaction mixture
was refuxed for 10–12 h and was cooled in ice bath followed
by fltration. Recrystallization was done in DMF to obtain
nitrone. In a recrystallization procedure, an impure nitrone was
dissolved in a hot DMF. As the solution was cooled, the pure
product crystallized out and the impurities stayed dissolved.
General procedure for Kornblum oxidation
A mixture of DMSO (50 ml) and NaHCO3 (7.1 g, 84 mmol)
in a round bottom fask was thoroughly de-gassed and then
heated to 150 °C under nitrogen atmosphere. Then, one
portion of iodomethyl compound (16 mmol) was added
and the resulting mixture was allowed to stir at 150 °C for
about 20–50 min. TLC was run in petroleum ether–dichlo-
romethane (3:1) to monitor reaction progress. After reac-
tion completion, reaction content was cooled to 20 °C for
10 min. Et2O (100 ml) was added, followed by the addi-
tion of water (100 ml). Two layers were formed which
were then separated and the aqueous layer was further
extracted with diethyl ether. The combined organic layers
were washed with H2O and dried over MgSO4. Solvent
Preparation of carbonyl compound
The nitrone (0.07 mol) was decomposed in a separatory
funnel with 250–320 ml of 2 M HCI and 200 ml of ether.
1 3

Chemical Papers
was removed under reduced pressure to give carbonyl com-
pound (61–83%).
General procedure for periodic acid and vanadium
pentoxide in IL‑based oxidation
A solution of iodomethyl compound (30 mmol) and ionic
liquid [bmpy]PF6 (15 mL) was taken in a round bottom
fask, and then H5IO6 (36 mmol) and V2O5 (0.9 mmol)
were added to reaction solution at r.t. Reaction content
was heated at 70 °C with continuous stirring for about
4–9 h. Reaction progress was monitored by means of
TLC using EtOAc/n-hexane 1:9 as an eluent. After
completion of reaction, the product was extracted with
DCM (3 × 10 mL). The organic layer was isolated and
washed with 5% NaHCO3 solution (3 × 10 mL) and water
(3 × 10 mL) to make the pH neutral. Then, the organic
layer was dried over Na2SO4 and fltered. The carbonyl
compound was purifed through recrystallization from
hexane and ethyl acetate (solid product) or by distillation
(liquid product). In some cases, column chromatography
was required to purify product. In these cases, the solvent
was removed followed by column chromatography using
hexane/ethyl acetate (8:1) as eluent which aforded car-
bonyl compound (83–94%). The rest of the ionic liquid
and the catalyst were recovered by decantation of aqueous
hydrogen halide produced in the reaction and concentrated
under vacuum. Fresh substrates were then recharged to the
recovered catalytic system and then recycled under speci-
fed reaction parameters.
General procedure for Hass–Bender reaction
2-Nitropropane (0.33 g, 3.72 mmol) and sodium methoxide
(0.27 g, 5.01 mmol) were taken in a reaction fask having
30 mL of 2-propanol. The reaction mixture was refuxed
for 30 min and then allowed to cool at r.t. Reaction mixture
was then charged with iodomethyl compound (2.67 mmol)
and was stirred at room temperature for 4–5 h [TLC control
(EtOAc/n-hexane 1:9)]. Reaction content was concentrated
by evaporation of solvent by rotary evaporator and the resi-
due was extracted with water (45 mL) and dichloromethane
(315 mL). The organic layer was dehydrated by anhydrous
MgSO4 and concentrated in vacuo. Further purifcation of
residue was performed by column chromatography on silica
gel using hexane/ethyl acetate (8:1) as eluent to aford car-
bonyl compound (49–83%).
General procedure for periodic acid in IL‑based
oxidation
To a stirred solution of iodomethyl compound (30 mmol)
in [C12mim][FeCl4] (1.2 mmol), H5IO6 (33 mmol) was
added and the reaction mixture was left on stirring at the
temperature of 50 °C for an appropriate time (3–5 h). The
reaction progress was monitored by means of TLC using
EtOAc/n-hexane 1:9 solvent system. After reaction com-
pletion, the reaction mixture was extracted with dichlo-
romethane (3×10 mL). The dichloromethane solution was
washed with 5% sodiumbicarbonate (NaHCO3) and dried
over anhydrous Na2SO4. The carbonyl compound was puri-
fed through recrystallization from hexane and ethyl acetate
(solid product) or by distillation (liquid product). In some
cases, column chromatography was required to purify prod-
uct. In these cases, the solvent was removed and the residue
was purifed by column chromatography using hexane/ethyl
acetate (8:1) as mobile phase to give carbonyl compound
(78–92%). Remaining ionic liquid and the catalyst were
recovered by decantation of aqueous hydrogen halide pro-
duced in the reaction and concentrated under vacuum. Fresh
substrates were then recharged to the recovered catalytic sys-
tem and then recycled under identical reaction conditions.
General procedure for Chunbao protocol
A mixture of iodomethyl compound (3 mmol), H2O
(30 mL), H2O2 (30%, 18 mmol), V2O5 (0.06 mmol) and
Aliquat 336 (0.6 mmol) was refuxed for 6–10 h [TLC
control (EtOAc/n-hexane 1:9)]. After cooling at room
temperature, two layers were observed (organic layer and
aqueous layer). The organic phase was separated and con-
centrated to aford pure carbonyl compound. In the case
of cinnamaldehyde, the chromatographic purifcation was
also performed. The crude cinnamaldehyde was purifed
via silica gel-based chromatographic purifcation tech-
nique, in which ethyl acetate in hexanes (1:2) as eluent was
employed to aford desired carbonyl compound (81–92%).
The aqueous phase was reused under identical reaction
conditions.
Note In some cases of Chunbao protocol, after reaction
completion, the organic layer was observed to be very thin;
in that cases, it is recommended to add Et2O (10 ml) in
order to get assistance for separation from aqueous phase.
For the large-scale preparation of carbonyl compounds
from the respective iodomethyl compound, the iodomethyl
compound must be added in small portions or dropwise.
1 3

Chemical Papers
Goswami S, Jana S, Dey S, Adak AK (2005) A simple and conveni-
ent manganese dioxide oxidation of benzyl halides to aromatic
aldehydes under neutral condition. Chem Lett 34:194–195. https
://doi.org/10.1246/cl.2005.194
General procedure for Khodaei method
TBAF (0.474 g, 1.5 mmol) and Bi(NO3)3·5H2O (1.6 g,
3.3 mmol) were taken in a reaction fask. Then, iodomethyl
compound (3 mmol) was added to the reaction vessel and
reaction mixture was stirred at 100 °C for about 1–2 h. Com-
pletion of the reaction was confrmed by TLC in EtOAc/n-
hexane 1:9 solvent system. Then, the mixture was cooled to
r.t and extracted with diethylether (2×10 mL). The organic
layer was isolated and further extracted with water followed
by drying over anhydrous sodium sulfate. Solvent was evap-
orated in vacuo and crude product was purifed by chroma-
tography (column size: 19×200 mm) over silica gel (70–230
mesh; EtOAc–hexane, 1:9) aforded the carbonyl compound
in 78–89% yield. In some cases, column chromatography
was not required to purify product. In these cases, evapora-
tion of solvent under vacuo aforded pure product.
Gupta N, Thakur A, Bhardwaj P (2014) Oxidative transformation of
alcohols and organic halides in aqueous solution. New J Chem
38:3749. https://doi.org/10.1039/C4NJ00393D
Hass HB, Bender ML (1949) The reaction of benzyl halides with the
sodium salt of 2-Nitropropane. 1 A general synthesis of substi-
tuted benzaldehydes. J Am Chem Soc 7:1767–1769. https://doi.
org/10.1021/ja01173a066
Hu YL, Liu QF, Lu TT, Lu M (2010a) Highly efcient oxidation
of organic halides to aldehydes and ketones with H5IO6 in
ionic liquid [C12mim][FeCl4]. Cat Comm 11:923. https://doi.
org/10.1016/j.catcom.2010.03.017
Hu YL, Liu X, Lu M, Jiang H (2010b) Efcient and convenient oxi-
dation of organic halides to aldehydes and ketones catalyzed by
H5IO6/V2O5 in ionic liquid [bmpy][PF6]. J Chin Chem Soc
57:28–33. https://doi.org/10.1002/jccs.201000005
Itoh A, Kodana T, Inagaki S, Masaki Y (2000) Photooxidation of
arylmethyl bromides with mesoporous silica FSM-16. Org Lett
2:2455–2457. https://doi.org/10.1021/ol0061081
Khodaei MM, Khosropour AR, Jowkar M (2005) Bi (NO3) 3·
Compliance with ethical standards
5H
2O-TBAF as an efcient reagent for in situ oxidation: dihy-
dropyrimidinone formation from benzyl halides. Syn 2005:1301–
1304. https://doi.org/10.1055/s-2005-861876
Conflict of interest The authors declare that they have no confict of
interest.
Kornblum N, Jones WJ, Anderson GJ (1959) A new and selective
method of oxidation. The conversion of alkyl halides and alkyl
tosylates to aldehydes. J Am Chem Soc 81:4113–4114. https://
doi.org/10.1021/ja01524a080
References
Krohnke F (1963) Syntheses using pyridinium salts (IV). Angew Chem
Int Ed 2:380–393. https://doi.org/10.1002/anie.196303801
Larock RC (1989) Comprehensive organic transformations. VCH Pub-
lication, NewYork
Alvarez-Manzaneda EJ, Chahboun R, Torres EC, Alvarez E, Alvarez-
Manzaneda R, Haidour A, López JR (2005) Reaction of allylic
and benzylic alcohols and esters with PPh3/I2: one-pot synthesis
of β, γ-unsaturated compounds. Tetrahedron Lett 46:3755–3759.
https://doi.org/10.1016/j.tetlet.2005.03.132
Li C, Zheng P, Li J, Zhang H, Cui Y, Shao Q, Ji X, Zhang J, Zhao P,
Xu Y (2003) The dual roles of oxodiperoxovanadate both as a
nucleophile and an oxidant in the green oxidation of benzyl alco-
hols or benzyl halides to aldehydes and ketones. Angew Chem Int
Ed 42:5063. https://doi.org/10.1002/anie.200351902
Armarego W, Chai C (2012) Purifcation of laboratory chemicals, vol
114. Elsevier, Kidlington. ISBN 9780123821614
LoPachin RM, Gavin T (2014) Molecular mechanisms of aldehyde
toxicity: a chemical perspective. Chem Res Toxi 27:1081–1091.
https://doi.org/10.1021/tx5001046
Backvall JE, Akermark B, Ljunggren SO (1979) Stereochemistry and
mechanism for the palladium (II)-catalyzed oxidation of ethene
in water (the Wacker process). J Am Chem Soc 101:2411–2416.
https://doi.org/10.1021/ja00503a029
Madathil R, Parkesh R, Draper SM (2006) Oligo (phenylene vinylene)–
poly (methylstyrene) hybrids: controlled step-wise molecular
wiring of oligo (phenylene vinylene). Tetrahedron Lett 47:2731–
2734. https://doi.org/10.1016/j.tetlet.2006.02.088
Barbry D, Champagne P (1996) Fast synthesis of aromatic aldehydes
from benzylic bromides without solvent under microwave irra-
diation. Tetrahedron Lett 37:7725. https://doi.org/10.1016/0040-
4039(96)01734-0
Marko IE, Giles PR, Tsukazaki M, Brown SM, Urch CJ (1996) Cop-
per-catalyzed oxidation of alcohols to aldehydes and ketones: an
efcient, aerobic alternative. Science 274:2044–2046. https://doi.
org/10.1126/science.274.5295.2044
Bayat A, Shakourian-Fard M, Ramezanpour S, Hashemi MM (2015)
A green procedure for direct oxidation of organic halides to alde-
hydes and ketones catalyzed by a molybdate-based catalyst. New
J Chem 39:3849–3851. https://doi.org/10.1039/C4NJ01886A
Benington F, Morin RD, Clark LC (1954) Mescaline analogs. I.
2,4,6-trialkoxy-β-phenethylamines. J Org Chem 19:11–16. https
://doi.org/10.1021/jo01366a003
Marson CM (1992) Reactions of carbonyl compounds with (mono-
halo) methyleniminium salts (vilsmeier reagents). Tetrahedrons
48:3659–3726. https://doi.org/10.1016/S0040-4020(01)92263-X
McKillop A, Ford ME (1974) An improved procedure for the conver-
sion of benzyl halides into benzaldehydes. Syn Comm 4:45–50.
https://doi.org/10.1080/00397917408062053
Cardilo P, Orena M, Sandri F (1976) Chromate ion as a synthetically
useful nucleophile: a novel synthesis of aldehydes from alkyl hal-
ides. J Chem Soc-Chem Comm 6:190. https://doi.org/10.1039/
C39760000190
Mukaiyama S, Inanga J, Yamaguchi M (1981) 4-Dimethylaminopyri-
dine N-oxide as an efcient oxidizing agent for alkyl halides. Bull
Chem Soc Jpn 54:2221. https://doi.org/10.1246/bcsj.54.2221
Palamone G, Poggio T, Kapeliouchko V, Laus M, Solvay specialty
polymers Italy SpA, (2011) Tetrafuoroethylene polymer particles.
U.S. Patent Application 11/739,145
Das S, Panigrahi AK, Maikap GC (2003) NaIO4–DMF: a novel
reagent for the oxidation of organic halides to carbonyl com-
pounds. Tetrahedron Lett 44:1375. https://doi.org/10.1016/S0040
-4039(02)02885-X
Porcheddu A, Colacino E, Cravotto G, Delogu F, De Luca L
(2017) Mechanically induced oxidation of alcohols to alde-
hydes and ketones in ambient air: revisiting TEMPO-assisted
Faisal M, Larik FA, Saeed A (2018) A highly promising approach for
the one-pot synthesis of biscoumarins using HY zeolite as recy-
clable and green catalyst. J Porous Mat. https://doi.org/10.1007/
s10934-018-0625-0
1 3

Chemical Papers
oxidations. Beilstein J Org Chem 13:2049. https://doi.
and potassium benzeneselenite. Syn 1984:747–751. https://doi.
org/10.1055/s-1984-30956
org/10.3762/bjoc.13.202
Rogers RD, Seddon KR (2005) Ionic liquids: fundamentals, progress,
challenges, and opportunities. American Chemical Society,
Washington
Wang A, Jiang H (2010) Palladium-catalyzed direct oxidation of alk-
enes with molecular oxygen: general and practical methods for
the preparation of 1, 2-diols, aldehydes, and ketones. J Org Chem
75:2321–2326. https://doi.org/10.1021/jo100125q
Stellman JM (1998) Encyclopaedia of occupational health and safety.
International Labour Ofce, Geneva
Wynberg N, Meijer EW (1982) The Reimer–Tiemann reaction. Org
React 28:1. https://doi.org/10.1002/0471264180
Syper L, Mlochowski J (1984) A convenient oxidation of halomethy-
larenes and alcohols to aldehydes with dimethyl selenoxide
1 3