Molecular Diversity

https://doi.org/10.1007/s11030-019-09956-1

SHORT REVIEW

Recent developments and comparison of transformation strategies

for organic halides to aldehydes and ketones
Muhammad Faisal1 · Aamer Saeed1 · Danish Shahzad1,2 · Parsa Dar1 · Fayaz Ali Larik1

Received: 7 December 2018 / Accepted: 8 May 2019

© Springer Nature Switzerland AG 2019

Abstract
Aldehydes and ketones are parts of millions of compounds and are important classes of chemicals which serve as important
precursors for the synthesis of library of compounds. For the synthesis of aldehydes and ketones, one impressive approach
to date, because of its excellent selectivity, high yield and stability toward over-reduction and over-oxidation, is the oxida-
tion of organic halides (viz. aliphatic and benzyl halides). The current review covers the conventional and eco-friendly
transformational approaches, from 2000 to date, toward synthesis of aldehydes and ketones from organic halides, including
mechanistic studies, comparison of different transformational strategies and discussion on scope and cons and pros of each
transformational approach. The review would be beneficial to get knowledge about recent synthesis techniques, select finest
synthetic approach, develop further new transformational methodologies and improve current transformational approaches.
Graphical abstract

Keywords Aldehydes · Ketones · Transformation · Oxidation · Benzyl halides · Conversion · Synthetic techniques

Extended author information available on the last page of the article

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Introduction
In chemistry, carbonyl group-containing organic com-
pounds, especially aldehydes and ketones, are the most
widespread, well-documented and important entities. The
importance of aldehydes and ketones cannot be concealed.
They are significant categories of chemicals that have been
extensively used as starting materials and precursors in the
synthesis of a series of special or fine chemicals, for
instance, sensors, nanomaterials, vitamins, drugs, fra-
grances, polymers, organic conductors, photochromic
materials and agrochemicals and dyes, etc. [1–4]. Moreo-
ver, aldehydes and ketones are parts of millions of com-
pounds and are widespread in nature; for example, many
aldehyde units are parts of essential oils and usually con-
tribute to their auspicious odors, for example, cilantro,
cinnamaldehyde, and vanillin [5, 6].
Aldehydes and ketones exhibit a central position in
the oxidation stages found among organic entities. They
are particularly desirable as functional groups because of
the wide range of their further transformations that are
possible. They could behave as electrophiles and also by
removing an alpha-proton; they could act as nucleophilic
species. These types of possible reactions make alde-
hydes and ketones potentially very useful as precursors
but complicate their preparation since they are usually
not very stable, mainly in oxidizing or basic environments
[7]. In general, there are two pathways for the prepara-
tion of aldehydes and ketones, viz. (1) direct methods:
in most cases, these methods are used for the synthesis
of aromatic aldehydes and ketones [8]. These approaches
involve the direct insertion of the carbonyl unit, or groups
directly changeable into it, into the aromatic core. The
most common and well-documented direct methods are
Blaise reaction, Friedel–Crafts reaction, Fries rearrange-
ment, Gattermann–Koch reaction, Duff’s hexamethylene-
tetramine reaction, reactions with N-methylformanilide,
chloral condensation, Reimer–Tiemann reaction, mercury
fulminate condensation, chloromethylene dibenzoate con-
densations, Vilsmeier–Haack reaction, isatin chloride con-
densations and treatment with organolithium compounds
[8–10], and (2) indirect methods: the indirect methods
offer the transformations of group or groups already pre-
sent in the compound into aldehyde or ketone function-
alities. The most common and well-documented indirect
methods are Bouveault aldehyde synthesis, Corey–Kim
oxidation, Dakin–West reaction, Tiffeneau–Demjanov
rearrangement, Dess–Martin periodinane oxidation,
Fukuyama reduction, McFadyen–Stevens reduction, Mof-
fatt oxidation, Nef reaction, Oppenauer oxidation, Pinacol
rearrangement, Rosenmund reduction, Rupe rearrange-
ment, Sommelet reaction and Swern oxidation [8–10]. In
13
Molecular Diversity
selecting any one of the approaches to prepare an aromatic
aldehyde or ketone, it is vital to consider the effect of sub-
stituent or substituents already situated in the core, since
they influence the ring activation, deactivation or orienta-
tion and side-reactions with the reagents [8, 11, 12]. In the
world of organic synthesis, indirect methods are more
useful than direct methods [11, 12]. It is because direct
methods are highly dependent on ring substituent effect.
The substituent effects cause ortho-directing, para-direct-
ing, meta-directing, ring activating or deactivating effects,
which result in formation of a number of by-products, low
yields and help the reactions to proceed slowly. Moreover,
in some cases, direct methods lead to the insertion of more
than one carbonyl group on ring nucleus. Literature survey
reveals that extensive amount of research work deals with
indirect methods [8].
Since the discovery of the popular indirect method, i.e.,
Sommelet reaction in 1913 [13], the oxidation of organic
halides (viz. aliphatic and benzyl halides) to the aldehyde
and ketone units represents one of the significant reactions
in organic synthesis [14]. Among all indirect methods, one
of the most suitable methods for synthesizing carbonyl com-
pounds is the transformation of organic halides to aldehyde
and ketones. There are two reasons for the suitability of this
reaction, i.e., (i) it avoids over-oxidation and over-reduction,
which is common in indirect methods, for example, in the
case of transformation of organic alcohols to organic alde-
hydes or ketones, over-oxidation is very common, while
in the case of transformation of organic acids or esters to
organic aldehydes or ketones, over-reduction is very frequent
[15], (ii) usually, organic halides-mediated transformation
provides high selectivity [14], and (iii) in most cases excel-
lent yields (> 90%) can be obtained [8, 14]. The function-
alization of benzylic halides into aldehydes and ketones is
a famous technique in the world of organic synthesis, while
the functionalization of aliphatic halides to aldehydes and
ketones is more tedious than benzylic halides oxidation.
Benzylic halides are easily synthesized via Blanc chloro-
methylation reaction [16] or by the photo-halogenation of
aromatic methyl groups [17]. Therefore, the synthesis of
aromatic aldehydes or ketones from organic halides is a
valuable pathway and to date, numerous procedures have
been established to perform this transformation. The well-
documented classical approaches for this conversion are
shown in Table 1 [18]. Herein, transformational approaches
during the period 2000 to date have been described. In other
words, this review deals with recent and modern transfor-
mational methodologies toward the preparation of aldehydes
and ketones from organic halides. This review summarizes
and discusses the scope and limitation of each approach.
To explain the transformation process, proposed mechanism
of each synthetic protocol is illustrated this review as well.
Moreover, table for the comparison of all transformational
Molecular Diversity

protocols has also been displayed, which provides an exten-
sive summary of each approach. The purpose of this effort
is to help chemist carrying out routine operations in organic
synthesis in the laboratory. It is expected that this review
will be very helpful in future research.
Classical synthetic approaches
Sodium metaperiodate in DMF
An efficient strategy for the preparation of series of alde-
hydes and ketones 2 from oxidation of primary and second-
ary halides 1 was illustrated by Sasmita Das and co-workers
(Scheme 1). In this approach, sodium metaperiodate (NaIO4)
in dimethylformamide (DMF) at 150 °C was employed,
which converted numerous primary and secondary organic
halides 1 to their respective aldehydes and ketones 2 within
40–60 min in excellent yields (70–90%) [19].
The plausible mechanism is outlined in Scheme 2. Briefly,
DMF enhances the nucleophilicity of NaIO4. The DMF-
NaIO4-based nucleophile 3 attacks on positively charged
(electrophilic) carbon of organic halide, leading to formation
of intermediate 4 and bromine ion (Scheme 2). The resulting
Br− ion then behaves as a base in the elimination reaction to
afford the carbonyl units [19].
The significance of NaIO4 in organic synthesis provoked
chemists to investigate the behavior of NaIO4 and DMF on
different halogen containing species. Recently, Tamilavan
et al. applied the concept of oxidation by NaIO4 in DMF for
synthesis of dialdehyde compound 6 from dibromo com-
pound 5. Oxidation of 4,7-bis(bromomethyl)benzo[c] [1, 2,

Table 1 List of famous classical Name or reagent of synthetic approach References Name or reagent of synthetic approach References
approaches for synthesis of
aromatic aldehydes or ketones Sommelet reactions [13, 61] Nitronate anion with Pd(PPh3)4 [62]
from organic halides
Hass–Bender oxidation [30, 63] Potassium chromate [64]
Krohnke method [65] Mercury-ethanolic alkali [66]
Kornblum method [67] Silver nitrate [68]
Amine oxide [69] NaOCl [70]
Dimethyl sulfoxide [48, 71] Bis(tetrabutylammonium)dichromate [72]
N-Alkoxypyridinium salts [48, 73] Electroreduced Fe (CO)5 [74]
Polymer supported reagents [75] Copper (I) chloride/kieselguhr [76]
Pyrazinyl sulfoxide [77] Carbon monoxide and tin hydride [78]
catalyzed by palladium
Dimethyl selenoxide [79] Transition metal complexes [80]

Scheme 1 Reaction of primary and secondary halides with NaIO4-DMF

Scheme 2 Proposed mechanism of oxidation by NaIO4 in DMF

13

Scheme 3 Synthesis of dialde-
hyde with NaIO4 in DMF
5] thiadiazole 5 with sodium periodate in DMF at 150 °C for
60 min under argon atmosphere furnished benzo[c] [1, 2, 5]
thiadiazole-4,7-dicarbaldehyde 6 in 59% yield (Scheme 3)
[20]. Li et al. used two step protocol for the synthesis of
benzo[c] [1, 2, 5] thiadiazole-4,7-dicarbaldehyde 6, i.e.,
NBS-promoted bromination followed by silver nitrate-pro-
moted hydrolysis. The overall yield was 55%. Hence, it is
concluded that, in single step, NaIO4 protocol provides bet-
ter yield [21].
3,6‑ Bis(triphenylphosphonium)cyclohexen
e peroxodisulfate in dilute acetonitrile
Badri et al. disclosed selective functionalization of organic
halides 1 to their respective aldehydes and ketones 2 with
3,6-bis(triphenylphosphonium)cyclohexene peroxodisul-
fate (BTPCP) 7 under neutral and mild reaction conditions
(MeCN/H2O reflux for 22–45 min) (Scheme 4) [22]. High
yields (43–97%) were observed in this protocol. The influ-
ence of different solvents on reaction, for example, ACN,
DMSO, CCl4, DMF, CHCl3 and DCM, was also tested [23,
24]. The results of experiment display that ACN was the
best solvent for this conversion. BTPCP 7 was found to be
a highly selective and operative oxidizer. Features such as
excellent yields (in most cases), neutral and mild conditions,
chemoselectivity and easy workup make this approach a sig-
nificant alternate technique for the transformation of primary
and secondary organic substrates to their respective carbonyl
entities. An interesting feature of BTPCP 7 was found to be
Scheme 4 Organic halides oxidation with BTPCP
13
Molecular Diversity
that it can also transform various benzyl amines and benzyl
nitriles to their respective carbonyl units [22]. However, it
was investigated that only benzylic substrates were trans-
ferred to their respective carbonyl units.
The plausible mechanism is displayed in Scheme 5. By
single electron transfer (SET) process, phenyl radical cation
9 is generated, which subsequently rearranges to produce
neutral benzyl radical intermediate 10. Reaction of interme-
diate 10 again with 8 affords benzyl cation 11, which imme-
diately couples with H2O to form cation 12 (Scheme 5).
Ultimately, the rearrangement in cation 12 generates ben-
zaldehyde [22].
Manganese dioxide in chloroform
Manganese dioxide (MnO2) is an inexpensive, convenient
and readily available oxidant, which is widely used in the
literature for oxidation purpose [25]. Goswami and co-
workers described a convenient, simple, efficient, mild and
cheap method for oxidation of aromatic halides 1 to their
corresponding aldehydes 2 in moderate to excellent yields
(40–80%) by using manganese dioxide under neutral con-
ditions (MnO2 in refluxing CHCl3 for 2–6 h) (Scheme 6).
This method works well for an extensive variety of aro-
matic bromides 1, which can be directly functionalized to
the respective aldehydes 2 where several different func-
tional groups like methoxy, pivaloyl, carbethoxy and nitro,
etc, survived [25]. This technique was also effective for
Molecular Diversity

the preparation of polynuclear aromatic aldehydes. How-
ever, this protocol was not convenient for synthesis of
dialdehydes.
A plausible mechanistic route for development of alde-
hyde entities from MnO2 is pictured in Scheme 7. Prob-
ably, in refluxing conditions, the halo moiety of aromatic
halide is thermally displaced to produce a benzyl radical 13
via activated interaction with MnO2, which instantly
couples with the radical of oxygen of 14 to produce an
intermediate 15. This intermediate subsequently under-
goes abstraction of acidic hydrogen, followed by reductive
breakage of oxygen-manganese bond and abstraction of
OMnX, leading to development of organic aldehydes and
salt Mn(X)OH [25].
2‑ Dimethylamino‑ N,N‑ dimethylanilin
e N‑ oxide in methanol
Sridhar et al. reported a highly effective and novel reagent
for the synthesis of aldehydes [26]. The name of the rea-
gent was 2-dimethylamino-N,N-dimethylaniline N-oxide
17, in which the mutual orientation of the basic dimeth-
ylamino (NMe2) and the N-oxide moieties guarantees that
the dehydro-elimination step operates through the putative
cyclic 7-membered transition state 18 (Scheme 10) [26].

Scheme 5 A plausible mecha-

nistic pathway for aldehydes
and ketones synthesis

Scheme 6 Manganese dioxide in chloroform reaction for aldehydes synthesis

Scheme 7 A plausible mecha-

nistic pathway for formation of
aldehyde entities from MnO2

13

Scheme 8 Synthesis of 2-dimethylamino-N,N-dimethylaniline
N-oxide
It was envisaged by Sridhar et al. that incorporating the
basic dimethylamino moiety and the heteroatom-centered
nucleophile—in suitable mutual orientation—in the same
compound would increase reactivity and thereby result in
a procedure workable under relatively mild conditions.
Another significant reason for choosing the N-oxide was that
it provides comparatively hindered environment around the
basic NMe2 entity, which avoids quaternization with the sub-
strate halide. 17 was prepared in 72% yield by oxidizing the
tetramethyl-o-phenylenediamine 16 with 30% H2O2 in meth-
anol (Scheme 8). This reagent oxidized various primary ben-
zylic bromides 1 to the corresponding aromatic aldehydes 2
under relatively mild conditions (MeCN/25–50 °C/6–24 h)
in excellent yields (83–97%) (Scheme 9). The substrates
investigated include a series of substituted benzyl bro-
mides, as well as the phenacyl and the cinnamyl systems
[26]. The most activated compounds reacted with 17 at
room temperature, but for others compounds, slight heat-
ing was required for 6–24 h. n-Hexadecyl bromide, n-heptyl
Scheme 9 Synthesis of aldehydes with 2-dimethylamino-N,N-dimethylaniline N-oxide
Scheme 10 Mechanism of oxidation with 2-dimethylamino-N,N-dimethylaniline N-oxide
13
Molecular Diversity
bromide, 1-phenylethyl bromide and benzyl chloride did not
react with 17 even at refluxing condition. In comparison, tri-
methylamine N-oxide transformed a broader range of halides
to carbonyl compounds-including unactivated aliphatic com-
pounds but at very low yields (usually < 45% for activated
systems) [27]. The scope of the current technique employing
17 is thus comparable to that of the Kornblum reaction, but
the benefit of neutral reaction conditions is obviously a valu-
able addition to the existing procedure.
The purposed mechanism is pictured in Scheme 10. The
oxygen atom on 17, which is partially negatively charged
and can act as a nucleophile, attacks on positively charged
(electrophilic) carbon of organic halide, leading to forma-
tion of cyclic seven-membered transition state 18. The
dehydro-elimination step then affords carbonyl compounds
(Scheme 10). The mutual orientation of the basic NMe2 and
the N-oxide entities guarantees that the dehydro-elimination
step happens through the putative cyclic 7-membered transi-
tion state [26].
o‑ Iodoxybenzoic acid in DMSO
IBX 19 is inexpensive and is becoming an increasingly
well-known oxidant owing to its environmentally friendly
attributes [28]. In this regard, Moorthy et al. reported a pro-
tocol for transformation of variety of benzyl halides 1 to
the corresponding aldehydes/ketones 2 in respectable yields
(50–90%) by using IBX 19 (o-iodoxybenzoic acid) in DMSO
Molecular Diversity
Scheme 11 Synthesis of aldehydes and ketones by using IBX in DMSO
Scheme 12 A plausible mechanistic pathway synthesis of aldehydes
and ketones with o-iodoxybenzoic acid
at 65 °C for 0.5–10 h (Scheme 11) [29]. Noteworthy, DMSO
was suitably applied to achieve the transformation of organic
halides to the respective aldehydes or ketones in good to
excellent yields (50–90%) in neutral conditions. The condi-
tions of reaction were optimized with 4-iodobenzyl bromide.
Studies revealed that when the reactions were performed in
dimethyl sulfoxide in the existence of 2-3 equiv. of IBX 19
at temperature within range of 60–70 °C, high yield was
obtained (Scheme 11). When the organic halide was iodide
or bromide, the aldehydes and ketones can be attained in
good to excellent yields; however, the transformation did not
accomplish for all aliphatic halides and in the case of benzyl
chlorides, the reaction proceeded only sluggishly [29].
On the bases of product and by-products, the mechanism
of development of the aldehydes and ketones is depicted in
Scheme 12 [29]. The reaction of substituted benzyl bromide
20 results in formation of the adduct 22, probably through
the reaction of salt 21 with IBX 19 in the case of electron-
rich organic halides, for example, 1-bromomethyl-4-meth-
oxybenzene. In next step, adduct 22 might subsequently
decompose to the ketone or aldehyde and 2-iodosylbenzoic
acid (IBA) 19 (Scheme 12). An SN1 mechanism probably
operates for electron-rich organic halides, while an SN2
mechanism presumably applies for electron-deficient cases.
Therefore, in the case of electron-deficient organic halides,
the development of addition product 22 (k1) is the rate-deter-
mining step; having said that, in the case of electron-rich
organic halides, decomposition step (k2) is the rate-deter-
mining step [29].
2‑ Nitropropane with base in ethanol
This transformational reaction was initially discovered and
documented by Bender and Hass [30]. It was the preparation
of aromatic aldehydes via reaction of substituted organic
halides with sodium salt of 2-nitropropane (also known
as sodium nitropropane salt or sodium propane-nitronate)
[31]. Hence, this transformational reaction was named as
Hass–Bender reaction [32] or Hass–Bender oxidation [33].
In the literature, Hass–Bender oxidation has been utilized
for synthesis of numerous aldehydes. In 2004, Frølund
et al. [33] applied Hass–Bender oxidation for the synthesis
of substituted 2-naphthaldehyde (Scheme 13). Treatment
of substituted 2-(brommethyl)naphthalen 24 with 2-nitro-
propane 25 in the presence of NaOEt in ethanol afforded
substituted 2-naphthaldehyde 26 in 90–50% yield. In 2005,
Klein et al. [32] modified the Hass–Bender oxidation by
employing NaH (strong base). Reaction of 1-(bromomethyl)-
2-chlorobenzene 27 with 2-nitropropane 25 in the presence
of NaH furnished 2-chlorobenzaldehyde 37 in 100% yield
(Schemes 13, 14).
13

Scheme 13 Hass–Bender reaction of organic halides with 2-nitropropane and base
Scheme 14 Mechanism of Hass–Bender reaction
Scheme 15 Synthesis of aldehydes and ketones with FSM-16 under
photo-irradiation
Mechanism for the oxidation of organic halides with 2-
nitropropane 25 and base is depicted in Scheme 15.
Elimination reaction on 2-nitropropane 25 by NaH results
in the formation of powerful nucleophile, which attacks on
positively charged (electrophilic) carbon of organic hal-
ide to deliver intermediate 30. The subsequently abstrac-
tion of acidic hydrogen, followed by reductive breakage of
oxygen–nitrogen bond in 30, leads to the development of
organic aldehydes [32].
Mesoporous silica FSM‑ 16 under
photo‑ irradiation
Akichika Itoh and co-workers described application of
mesoporous silica FSM-16 for the synthesis of carbonyl
compounds. A mesoporous silica FSM-16 (folded sheets
mesoporous materials) was observed to be a recyclable
13
Molecular Diversity
transformational oxidant of organic bromides 1 for the
synthesis the respective aldehydes or ketones 2 in 32–72%
yield under photo-irradiation conditions in the existence of
acetone as solvent at 25 °C (Scheme 15) [34]. This was
environmentally friendly method owing to following two
impressive features: (i) the application of a recyclable solid
catalyst in the place of heavy metals and (ii) one-pot tech-
nique. Additionally, this technique was very simple from
the point of view of the suitability of the easy workup, i.e.,
FSM-16 could be separated easily from reaction mixture
through filtration technique [34]. However, aldehydes are
actually minor products in most cases with the correspond-
ing acids as the majority.
Pyridine N‑ oxide with silver oxide in
acetonitrile
An convenient and efficient strategy for the preparation of a
variety aromatic and α,β-unsaturated carbonyl compounds
2 in excellent yields (74–95%) from benzylic and allylic
halides 1, respectively, by pyridine N-oxide 31 in the exist-
ence of Ag2O under mild reaction conditions (CH3CN,
stirring overnight under N2 at 25–50 °C) was illustrated by
David X. Chen and co-workers (Scheme 16) [35]. Among
ACN, toluene and THF, investigation revealed that when
the reaction was carried out in acetonitrile, excellent yields
were obtained. Also, in the case of organic bromides, the
transformational reactions were efficiently performed at
25 °C and the oxidation was observed to be completed in
4–8 h; however, for convenience purpose, reaction was
stirred overnight. Slightly elevated temperature (nearly
Molecular Diversity
Scheme 16 Preparation of carbonyl compounds with pyridine N-oxide in Ag2O
50 °C) was required in the case of organic chlorides and
some benzyl bromides with very powerful deactivation
groups. Only partial transformation was also observed in
the case of some organic chlorides. The workup of trans-
formational reaction was very easy. Upon reaction comple-
tion, Na2SO4 or MgSO4 was added and the resulting con-
tents were filtered by a thin-layer of Celite. Concentration
under reduced pressure afforded pure aldehyde or ketone in
quantitative yield. For further purification purpose, when
required, the crude aldehyde or ketone was passed through
a short column of silica gel with DCM as the eluent.
Initially, the pyridine was removed from reaction mixture
in loaded column by washing with n-hexane [35]. Most
attractive feature of this strategy was that the approach was
somewhat independent of nature of groups (electron-
withdrawing group or deactivating group) pre- sent in
organic halides. The strategy defined here was thus a
valuable and suitable alternative to the existing approaches
for transformation of allylic and benzylic hal-
ides to aldehyde and ketone compounds.
Plausible mechanistic pathway for the synthesis of car-
bonyl compounds with pyridine N-oxide 31 in silver oxide
is illustrated in Scheme 17. In the substitution reaction with
31, Ag2O intensifies the heterolysis cleavage of the C–X
bond. The resulting OH− from the reaction between Ag2O
and halogen (X−) then operates as a base in the
unimolecular elimination reaction on 32 to furnish the
aldehyde or ketone [35].
Scheme 17 A plausible mecha-
nistic route for the preparation
of carbonyl compounds
Hydrogen peroxide in ethanol
A convenient and effective methodology for the transfor-
mation of organic halides to the aldehyde and ketone com-
pounds, in which hydrogen peroxide in refluxing EtOH was
employed as the oxidizer was described by Tang and co-
workers [36]. Numerous primary and secondary aromatic
bromides 1 were oxidatively transformed via hydrogen
peroxide (H2O2) in refluxing EtOH for 1–24 h to deliver
the respective aldehydes and ketones 2 in good to excel-
lent yields (up to 94%). Aromatic chlorides were oxidatively
transformed to their respective aldehydes and ketones via the
same oxidant (H2O2) in EtOH in the existence of 10 mol%
potassium bromide as the catalyst (Scheme 18) [36]. The
methodology functioned fine for numerous substituted
organic halides generating excellent yields (up to 94%) of
aromatic aldehydes or ketones. It was observed that 1 could
be oxidatively transform to 2 via H2O2 in refluxing EtOH
in 3 h. In other organic solvents, for example methylene
chloride, chloroform and tetrahydrofuran much longer time
was observed for conversion of reactant into product and the
transformation was poorer. However, on positive side, this
method offers a convenient way to synthesize substituted
aldehydes. Application of clean oxidizer hydrogen peroxide
together with non-toxic organic solvent EtOH makes this
technique environment friendly [36].
A plausible mechanistic pathway is displayed in
Scheme 19. Hydrolysis of organic halide 33 affords the
respective alcohol 34, which was then functionalizes to
hypobromite specie 35 through assistance of the bromanol
13

Scheme 18 Reaction of primary and secondary halides with hydrogen peroxide in ethanol
Scheme 19 Plausible mechanistic pathway for development of car-
bonyl compounds
(HOBr), which is produced in situ by the reaction of
hydrogen peroxide with HBr. This hypobromite specie 35,
on elimination of acid proton, generates the final alde-
hydes or ketones 36, with reproduction of HBr. In the case
of organic chlorides, catalytic addition of potassium bro-
mide is essential, to develop the actual oxidant, bromanol
(HOBr) (Scheme 19). It seems like the rate-determining
step is the hydrolysis of the organic halide because the
hydrolysis rate of primary halides is faster compared to that
of secondary halides [36].
Scheme 20 Synthesis of car-
bonyl units with QCC in NaOH
13
Molecular Diversity
Quinolinium chlorochromate with
dilute sodium hydroxide
An economical and valuable protocol for a one-pot trans-
formation of organic halides 1 to their respective aldehydes
or ketones 2 in 35–37% yield was illustrated by Gupta et al.
[37] using sodium hydroxide and quinolinium chlorochro-
mate (QCC) 37 in an aqueous solution without application of
any co-solvent at 54–50 °C for 8–18 h (Scheme 20). QCC 37
is a dark-yellow to light-brown solid, which is very stable in
aqueous medias for a large time span and not very sensitive
toward moisture [38]. Quinolinium cations in QCC 37 offer
stability and selectivity [39] to the reagent in comparison
with isoquinolinium and pyridinium derivatives, for exam-
ple, isoquinolinium chlorochromate (IQCC) and pyridinium
chlorochromate (PCC). In comparison with pyridinium ions,
quinolinium cations were larger in size and hence lesser
positive charge per area unit. This property stabilizes the
negative charge in the chromium center to a lesser extent.
The work of Gupta et al. also illustrated a well-organized
use of quinolinium chlorochromate 37 in the synthesis of
important natural products [37, 40].
Mechanistically, in the first step, the halides are trans-
formed into alcohols via nucleophilic substitution reaction
(Scheme 21). Next, the oxygen moiety in OH of alcohol 38
attacks on chromium(VI) atom of 37 to create a chromate
ester 39 by abstracting chlorine ion, which behaves as a base.
Molecular Diversity
Scheme 21 A plausible mechanistic pathway synthesis of carbonyl units with QCC in NaOH
Scheme 22 Synthesis of aldehydes and ketones with trimethylamine N-oxide
Removal of proton from 39 by chlorine ion leads to forma-
tion of aldehydes or ketones [37].
Eco‑ friendly synthetic approaches
Trimethylamine N‑ oxide
In the literature, trimethylamine N-oxide 40 (TMANO) has
been extensively used as an oxidizer for the transformation
of organic halides to carbonyl entities [41]. The solvents
used include CH3CN, CHCl3, DMF and DMSO. No oxida-
tion had been carried out in water, which is an environmen-
tally friendly solvent. Replacing organic solvents with H2O
would help to decrease the problems of environment related
with the oxidation. In this regard, Zheng et al. reported green
protocol for oxidation of benzyl halides 1 to the correspond-
ing aldehydes or ketones 2 using trimethylamine N-oxide
40 (TMANO) in aqueous media at refluxing conditions
for 0.25–6 h (Scheme 22). TMANO 40 produced in situ
from N(Me)3 and H2O2. The reaction yield was excellent
(80–94%), and the workup was also simple [42].
It was also investigated by Zheng et al. [42] that electron
-releasing groups (ERGs), for instance, –OR or –OH on aro-
matic structural centerpiece, result in higher rates of reac-
tion. Electron-withdrawing groups (EWGs), for instance,
–X or –NO2, substantially decreased the rates of reaction.
Ortho substituents and bulky species decreased the rates of
reaction. Usually, primary halides were functionalized faster
when compared with secondary halides. The rate of reaction
was faster with benzyl bromide when compared with benzyl
chloride.
Scheme 23 Proposed mechanism for the development of carbonyl
compounds with TMANO
Hence, this green approach has numerous advantages
over other classical approaches, i.e., (i) environmental
friendly H2O was used as reaction solvent and no organic
solvents were employed in the entire procedure, (ii)
N(Me) 3 and H2O2 were employed to produce TMANO
40 in situ and this prevented the direct use of TMANO
40, which makes the workup very simple, and (iii) in the
oxidation, no side-products were produced. The rate of
reaction was also high, and the reaction yield was nearly
quantitative. The product was simply isolated from H2O.
The mechanism of the functionalization of organic hal-
ides to ketones or aldehydes is illustrated in Scheme 23.
Trimethylamine and hydrogen peroxide under refluxing
conditions react to produce TMANO 40. The oxygen
moiety on TMANO 40 molecule is partially negatively
charged and can act as a powerful nucleophilic oxidizer
toward organic halides that were transformed into ketones
or aldehydes [42].
13

Bismuth(III) nitrate pentahydrate in TBAF
Bismuth(III) nitrate pentahydrate is an inexpensive, crystal-
line solid and commercially available reagent and requires
no special handling. A convenient method for the synthe-
sis of aldehydes 2 in 55–95% yield from alkyl halides 1
in the presence of Bi(NO3)3·5H2O as reagent in TBAF as
ionic liquid at 100 °C for 1–7 h was examined by Khodaei
and co-workers (Scheme 24) [43]. By taking benzyl bro-
mide as the substrates, synthesis of benzaldehyde was
performed with numerous ionic liquids in the existence of
Bi(NO3)3·5H2O. The investigation reveals that TBAF was
perfect an ionic liquid for benzyl bromide transformation.
Organic halides with substituents carrying either electron-
releasing or electron-donating groups reacted nearly quan-
titatively and afforded the aldehydes or ketones in excellent
purity. The efficiency of the reagent was studied through
the oxidative transformational reaction of benzyl bromide
2 in the absence of Bi(NO3)3·5H2O. No benzaldehyde was
observed in this reaction, which reveals that Bi(NO3)3·5H2O
had vital part in transformation. Application of 1.10 mmol
of Bi(NO3)3·5H2O was necessary and enough to push the
oxidative transformational reactions forward. Increasing
quantity of the Bi(NO3)3·5H2O did not improve the yield to
a greater extent. But, an increased amount of Bi(NO3)3·5H2O
that was 1.30 mmol, was desired for reaction completion
when 2-(chloromethyl)naphthalene used [43].
Hydrogen peroxide with vanadium
peroxide and Aliquat 336
Vanadium peroxide (V2O5) is involved in several impor-
tant transformational reactions [44]. Chunbao Li and co-
workers disclosed a green methodology for transformation
of organic halides 1 to aldehydes and ketones 2 in boiling
water for 5–24 h using hydrogen peroxide (H2O2) catalyzed
Scheme 24 Oxidation of halides with Bi(NO3)3·5H2O as catalyst in TBAF
13
Molecular Diversity
by vanadium peroxide (V2O5) and Starks’ catalyst (Aliquat
336) 41 (Scheme 25) [45]. This procedure afforded good
to excellent yields (32–85%) in most cases and was opera-
tionally simple. Moreover, it was suitable for a transforma-
tion of series of functionalized organic halides. Attributed
to high stability, cheapness, the presence of high oxygen
contents, H2O2 was used as the oxidizer. The catalysts
(V2O5 and Starks’ catalyst 41) were also cheap, stable and
effective and could be recycled without losing its effective-
ness (Scheme 25). In this transformational approach, only
H2O was employed for diluting the H2O2 and beauty of this
approach was that, in the whole process, no organic sol-
vents were employed. This green transformational approach
offered an excellent solution for the existing complications
in the functionalization of organic halides. One of the most
attractive features was the transformation of organic chlo-
rides into aldehydes was quantitative (> 90%). Hydrochloric
acid (HCl) and water were the two waste products in reac-
tion. The HCl offers acidic media to accelerate the transfor-
mational reaction. In the report by Chunbao Li and co-work-
ers, 20 organic halides were converted in excellent yields to
their respective ketones or aldehydes [46, 47]. The oxidative
transformation was also compatible with phenolic groups,
aryl halides, amides, ethers and esters. Primary organic hal-
ides were transformed faster than secondary organic halides,
which revealed that the anion, viz. OV(O2 )2−, was a bulky
nucleophile and was sensitive toward steric hindrance [45].
Benzyl bromides were transformed faster than benzyl chlo-
rides. Reason for this fact was that the OV(O2 )2− anion was
such a good leaving group that it was more easily substituted
by the better nucleophile, Br−, than by the Cl−.
A possible mechanism for the oxidative transformation of
halides is depicted in Scheme 26. In acidic solution, V2O5
can exist as VO2+ and VO3− at first. Addition of H2O2 to
VO + can give the red oxoperoxo VO(O )+ 42 and the yellow
2 2
oxodiperoxo VO(O2)−2 moieties 43, which react with halide
Molecular Diversity
Scheme 25 Green synthesis of carbonyl moieties with H2O2 catalyzed by V2O5 and Aliquat 336
Scheme 26 A plausible mecha-
nism for aldehydes and ketones
oxidation with H2O2 catalyzed
by V2O5 and Aliquat 336
to produce transition state 44 and then, 44 eliminates the
oxoperoxo 42 and proton to afford the desired product [45].
Microwave‑ assisted Kornblum reaction
Vital limitation of the Kornblum’s aldehyde synthesized
through classical approaches was the long reaction time at
room temperature to obtain good yields [26, 48–50]. Micro-
wave irradiation had been never applied to perform the
Kornblum’s aldehyde reaction. For the first time, Bratulescu
and co-workers modified the classical Kornblum’s reaction
by microwave irradiation [51]. The aromatic aldehydes 2
were synthesized in excellent yields (80–97%) by oxida-
tion of corresponding halides 1 with DMSO in NaHCO3 by
irradiation with microwave for 2–4 min (Scheme 27). The
reagents were mixed well to form a paste, which was irradi-
ated with assistance of microwaves. The excellent yields, the
purity of the products, the easy experimental procedure and
short microwave irradiation time of a few minutes were the
key advantages of this technique [51].
The plausible mechanism of transformational technique
is sketched in Scheme 28. The oxygen atom on 45 was par-
tially negatively charged and can act as a nucleophile. Under
microwave irradiation, the nucleophilic oxygen of 45 attacks
on positively charged (electrophilic) carbon of organic hal-
ide, leading to formation of intermediate 46. This interme-
diate 46 experiences subsequently loss of acidic hydrogen,
followed by reductive breakage of oxygen–sulfur bond
resulting in the formation of aromatic aldehydes and Me 2S,
H2O, CO2 and KBr as by-products [51].
Mg–Al hydrotalcites‑ catalyzed Kornblum
reaction
Kshirsagar et al. disclosed Mg–Al hydrotalcites (HTs) 47
for synthesis of library of aldehydes and ketones 2 [52].
Mg–Al HTs 47 act as an effective heterogeneous base cata-
lyst for the transformation of organic halides 1 to their cor-
responding aldehydes or ketones 2 in 60–92% yield using
DMSO as an oxidant at 140 °C for 1–12 h (Scheme 29).
The reaction was performed at various temperatures, and
13
 Molecular Diversity

Scheme 27 Kornblum reaction with microwave irradiation for synthesis of aldehydes

Scheme 28 Oxidation mechanism for the aldehydes construction with Kornblum reaction

Scheme 29 Aldehydes synthesis with Kornblum reaction catalyzed by Mg–Al hydrotalcites

it was observed that with increase in temperature of reac-
tion above 140 °C, there was a decrease in selectivity of
reaction, while with a decrease in temperature of reaction
(140–80 °C), the rate of reaction decreased. The transfor-
mational oxidation was performed by applying various
hydrotalcites (Mg4 Al2(OH) 24CO3, Mg 6 Al2(OH) 24 CO3,
Mg10Al2(OH)24CO3 and Mg6Al2(OH)24CO3) as well as clas-
sical bases (MgO, NaOH, Na2CO3 and NaHCO3) at 140 °C.
In comparison with the classical catalysts, the uncalcined
hydrotalcites (Mg/Al = 2, 3, 5) delivered better yields. The
reaction with NaOH (classical base) leads to the develop-
ment of benzoic acid and dibenzyl ether as a side-products,
while with Na2CO3 (classical base), phenylmethanol was the
major product. In the existence of Na2CO3 (classical base),
the reaction was sluggish. The reaction did not occur in the
absence of hydrotalcite 47. The key advantage of this reac-
tion was that the HT 47 is a heterogeneous catalyst, which
could easily be isolated from reaction contents through
filtration. The recovered catalyst for reaction could be effi-
ciently recycled for 5 successive runs.
Under the optimized conditions, numerous organic hal-
ides were reacted with DMSO to give their respective alde-
hydes and ketones. Under these conditions, simple aliphatic
halides, for instance, octyl chloride and propyl bromide, did
not undergo the transformation reaction. In this method,
there was no application of any separate oxidant such as
IBX 19, H2O2, periodate and peracid, but the DMSO was
used in excess. Hydrotalcite 47 and DMSO offer an opera-
tive combination for the transformation of organic halides
to aldehydes and ketones (Scheme 29) [52].
The plausible mechanism is outlined in Scheme 30. The
oxygen atom on 45 is partially negatively charged and can
act as a nucleophile. The nucleophilic oxygen of 45 attacks
on positively charged (electrophilic) carbon of organic hal-
ide, leading to formation of intermediate 48 (Scheme 30).
This intermediate 48 undergoes subsequently loss of acidic

13
Molecular Diversity
Scheme 30 Mechanism of
oxidation by Kornblum reaction
catalyzed by Mg–Al hydrotal-
cites
hydrogen, followed by reductive breakage of oxygen–sulfur
bond, resulting in the formation of aromatic aldehydes [52].
Potassium nitrate with CTAB
Phase-transfer catalysis (PTC) is a versatile synthetic
technique that has been widely applied to enhance oth-
erwise slow heterogeneous reactions, including an ionic
reactant and an organic substrate, either present in solid
state (solid–liquid) or dissolved in water (liquid–liquid)
[53]. Furthermore, PTC can intensify the effectiveness of
organic synthesis, can reduce consumption of raw materi-
als and organic solvent, can efficiently avoid side-reactions
and can make reaction conditions gentle. To date, PTC had
been used in numerous organic syntheses; for example,
hydrolysis, oxidation reaction, nucleophilic substitution
reaction and electrophilic substitution reaction [53, 54]. In
this regard, Liu et al. disclosed a new, eco-friendly, conveni-
ent and economic technique for the synthesis of aromatic
ketones and aldehydes 2 from organic halides 1 in aqueous
media at refluxing conditions for 0.25–10 h by using phase-
transfer catalyst (CTAB: cetyltrimethylammonium bromide)
49 combined with 10% aqueous potassium hydroxide solu-
tion (KOH) and potassium nitrate (KNO3) (Scheme 31) [55].
These mild reaction conditions provided moderate to good
yields (35–92%). In this catalytic oxidation system, besides
CTAB 49, inquiry of other PTCs, viz. dodecyltrimethylam-
monium bromide (DTAB), tetrabutylammonium bromide
Scheme 31 Reaction of organic halides with KNO3 and KOH catalyzed by CTAB
(TBAB) and tetraethylammonium bromide (TEAB), was
also performed. However, the yields were merely 80%, 71%
and 53%, respectively. The best PTC was CTAB 49. Judging
from the reaction conditions used, this oxidation technique
displayed had great prospects in commercial applications
[55].
The present reaction mechanism of oxidation is well
documented in the literature [53, 54]. Organic halides are
first converted to their respective nitrate esters 50 via reac-
tion with aqueous KNO3 solutions in the presence of CTAB
49 and then transforms into their respective aldehydes or
ketones and potassium nitrite as a by-product under the syn-
ergism of KOH and PTC 49 (Scheme 32) [55].
Periodic acid and vanadium pentoxide in
BMIM‑ PF6
A eco-friendly, efficient and mild technique for the trans-
formation of organic halides 1 to their respective aldehydes
and ketones 2 in good to high yields (24–98%) catalyzed by
H5IO6/V2O5 in ionic liquid, viz. 1-butyl-3-methylimidazo-
lium hexafluorophosphate, (abbreviated as [bmpy][PF6] and
BMIM-PF6) 51 at 50 °C for 3–24 h, with no trace of over-
oxidation to acids, was reported by Ming Lu and co-workers
(Scheme 33) [56]. By a simple extraction in separating fun-
nel with organic solvent, the synthesized product could be
separated. Further, handling of catalytic system was very
simple and can be reused or recycled without any impor-
tant loss of catalytic efficiency [57, 58]. This procedure
13

provides many exclusive physicochemical characteristics, for
instance, wide electrochemical window, large liquid range,
large thermal stability, excellent capacity to dissolve many
chemicals and negligible flammability and volatility under
ambient conditions [56]. The mechanism of this approach is
similar to as described in Scheme 26.
Periodic acid in [C12mim][FeCl4]
A efficient, mild and simple process for the selective func-
tionalization of organic halides 1 to aldehydes and ketones
2 with H5IO6 in ionic liquid, viz. 1-dodecyl-3-methylimida-
zolium iron chloride [C12mim][FeCl4] 55 under mild reac-
tion conditions (30 °C, 1.5–3 h) was lettered by Yu Lin Hu
and co-workers (Scheme 34). The oxidative transformational
reactions delivered the target aldehydes and ketones in good
Scheme 32 Oxidation mecha-
nism with KNO3 and KOH
catalyzed by CTAB
Scheme 33 Functionalization of organic halides to carbonyl entities with H5IO6/V2O5 in ionic liquid
Scheme 34 Selective oxidation of halides with periodic acid in ionic liquid
13
Molecular Diversity
to excellent yields (88–96%), and no over-oxidation to acid
was observed [59].
Hydrogen peroxide with Mag‑ Mo
magnetic catalyst
One of the most well-organized, effective and efficient strate-
gies for the synthesis of series of carbonyl compounds 2 was
illustrated by Bayat et al. which was based on molybdate-based
heterogeneous magnetic catalyst 56 (abbreviated as Mag-Mo
catalyst) (Fig. 1) [60]. A Mag-Mo catalyst 56 was prepared and
applied in direct transformation of numerous 1° and 2° organic
halides 1 to their respective organic aldehydes and ketones 2 in
60–95% yield using 30% H2O2 as oxidant in refluxing ethanol
for 4–9 h (Scheme 35). The Mag-Mo catalyst could be eas-
ily removed from reaction mixture by employing an external
magnet and recycled in 6 runs without any important loss of
Molecular Diversity

Fig. 1 Structure of molybdate-

based heterogeneous magnetic
catalyst

Scheme 35 Synthesis of aldehydes and ketones with H2O2 catalyzed by Mag-Mo catalyst

catalytic potency. Hydrogen peroxide was an effective cheap in which H2O2 was used can be controlled easily as compare
and non-toxic oxidizer. Furthermore, the reaction of oxidation to molecular oxygen and air [60].

13
 Molecular Diversity

Table 2 Summary of features and limitation

Protocol name Average Recyclability Reported feature(s) Reported limitation(s)

yield
(%)

NaIO4 in DMF 83 No Applicable for di- and aliphatic alde- No limitation reported
hyde synthesis
BTPCP in MeCN 79 No Excellent selectivity, neutral conditions, Only applicable for benzylic substrates
easy workup,
MnO2 in CHCl3 59 No Readily available, cheap oxidant, Not convenient for synthesis of dialde-
synthesis of polynuclear aromatic hyde
aldehydes
TMANO in H2O 88 No Green protocol, environmentally benign No limitation reported
solvent, simple workup
75 in MeCN 90 No Able to prevents quaternization with Benzyl chloride, 1-phenylethyl bromide
reactant halide, mild conditions and n-heptyl bromide do not react
Bi(NO3)3·5H2O in TBAF 86 No Inexpensive, commercially available No limitation reported
reagent, no special handling
H2O2 in V2O5 and Aliquat-336 76 Yes Green oxidation, stable, inexpensive, Large number of reagents used, expen-
Suitable for organic chlorides oxida- sive reagents
tion
Kornblum reaction in microwave 88 No Microwave irradiation, short irradiation No limitation reported
time, easy experimental protocol
Kornblum reaction in Mg–Al HT 81 Yes (5 runs) Catalyst easily can be separated from Not applicable for aliphatic halides (pro-
reaction contents by filtration pyl bromide and octyl chloride)
IBX in DMSO 71 No Cheap reagent, protocol was environ- Not applicable for aliphatic halides and
mentally benign benzyl chlorides
KNO3 and KOH 78 No Economic, convenient, and eco-friendly Not applicable for aliphatic halides
method
Hass and Bender 73 No Quantitative yield, applicable aliphatic Limited scope
aldehyde synthesis
FSM-16 under hv 54 Yes Environmentally friendly, FSM-16 can Applicable only for limited cases
be easily removed only by filtration
pyridine N-oxide in Ag2O 84 No Applicable for electron-donating and Difficulty in crude product separation
-withdrawing substituents
H2O2 in EtOH 81 No Clean oxidant, non-toxic solvent Not applicable for aliphatic halides (177)
H5IO6/V2O5 in [bmpy][PF6] 91 Yes no trace of over-oxidation, easy to Large number of reagents used, expen-
handle, applicable aliphatic aldehyde sive reagents
and ketone synthesis
H5IO6 in [C12mim][FeCl4] 94 Yes Excellent selectivity, no trace of over- Expensive reagents
oxidation, easy to handle, applicable
aliphatic aldehyde/ketone synthesis
H2O2 in Mag-Mo 85 Yes (6 runs) Catalyst separated by using external Large number of steps to synthesized
magnet, non-toxic, applicable ali- catalyst
phatic aldehyde and ketone synthesis
QCC with NaOH 37 No Economical, oxidant not sensitive to Limited scope
moisture

Summary and comparison of taking average of yields of synthesized products, which

different transformational
approaches
To deduce the relative cons and pros of different oxida-
tion approaches toward functionalization of organic hal-
ides to aldehydes and ketones, comparison table has been
constructed (Table 2). This table provides a quick review
about the scope and applicability of different protocols. In
Table 2, average yields of approaches are estimated by
13
were reported by the author(s) of that research paper.
Next comparison is based on yields of benzalde-
hyde that are obtained via different transformational
approaches. Treatment of (bromomethyl)benzene 57 or
(chloromethyl)benzene 58 with different oxidizing proto-
cols afforded benzaldehyde (Table 3). The yield of this
reaction depends on capability of that protocol. The aim
of the table is to disclose relative capability of different
Molecular Diversity

Table 3 Scope of different transformational approaches toward oxidation of 57 and 58

Reagents Solvent Temp (°C) Time Yield (%)a Yield (%)b

NaIO4 DMF 150 40 min 80

BTPCP MeCN in H2O Reflux temp 24 min 93 97
MnO2 CHCl3 Reflux temp 2 h for 2, 6 h for 22 80 40
TMANO H2O Reflux temp 0.25 h for 2, 0.5 h for 22 80 82
75 MeCN 50 8 83
Bi(NO3)3·5H2O in TBAF 100 1 h for 2, 1.5 h for 22 91 90
H2O2, V2O5, Aliquat 336 H2O Reflux temp 14 h for 2, 6 h for 22 84 70
Me2SO, NaHCO3 Microwave 2.5 min for 2 93
Mg-Al HTs DMSO 140 6 h for 2, 10 h for 22 82 80
KNO3, KOH, CTAB H2O Reflux temp 3 91 90
Pyridine N-oxide, Ag2O CH3CN 25 Stirring overnight 82
H2O2 EtOH Reflux temp 3 h for 2, 3.5 h for 22 89 82
H5IO6/V2O5 [bmpy] [PF6] 50 3 h for 22 92
H5IO6 [C12mim] [FeCl4] 30 2h 94
QCC, NaOH H2O Reflux temp 8h 38
a
Yield of product of oxidation of 57
b
Yield of product of oxidation of 58

oxidation protocols toward oxidation of organic halides to
aldehydes and ketones.
Conclusion and future prospects
The aim of this review is to point out recent advances in the
field of synthesis of aldehydes and ketones, to encourage
the chemists to design and develop new transformational
strategies and to help chemist carrying out routine reactions
in organic synthesis in a laboratory. The review deduced
that the recent and modern transformational approaches are
better than classical approaches. These approaches contain
unique features such as recyclability of catalytic systems,
quantitative yields, cheapness and so forth that are not pre-
sent in previous classical approaches. These transformations
also can avoid over-oxidation and provide excellent yields
and selectivities. Most importantly, these approaches con-
tain features of eco-friendly and sustainable chemistry, i.e.,
microwave-promoted synthesis, ionic liquid-based synthesis
and water as solvent-mediated synthesis.
Firstly, we give a smart summing-up for all the trans-
formational methods. Among all transformational methods,
NaIO4 in DMF, MnO2 in CHCl3 and TMANO in H2O are
the cheapest methodologies, while TMANO in H2O, H2O2
in Mag-Mo, H2O2 in EtOH and H2O2 in V2O5 and Ali-
quat-336 are environment-friendly methodologies. Further,
Bi(NO3)3·5H2O in TBAF, H5IO6/V2O5 in [bmpy][PF6] and
H5IO6 in [C12mim][FeCl4] are ionic liquid-promoted meth-
odologies, whereas H2O2 in Mag-Mo, H5IO6/V2O5 in [bmpy]
[PF6], FSM-16 under hv, Kornblum reaction in Mg–Al HT
and H2O2 in V2O5 and Aliquat-336 have characteristic of
catalyst recyclability. In addition, the methodologies which
provide high yields in most cases are H5IO6 in [C12mim]
[FeCl4], H5IO6/V2O5 in [bmpy][PF6] and 2-dimethylamino-
N,N-dimethylaniline N-oxide in ACN. It is also observed
that bromo-halides give better results than chloro-halides.
Moreover, BTPCP in MeCN and H5IO6 in [C12mim][FeCl4]
demonstrates excellent selectivities in most cases and H5IO6/
V2O5 in ionic liquid [bmpy][PF6], H5IO6 in ionic liquid
[C12mim][FeCl4] and H2O2 catalyzed by Mag-Mo catalyst
are most suitable for synthesis of aliphatic aldehydes and
ketones in good yield.
The authors of review also conclude that there are fol-
lowing six features, which make transformational approach
highly efficient and well organized: (i) synthetic protocol
must be economical and recyclable, (ii) green synthesis
is the prime requirement of modern chemistry; therefore,
transformational approach must be environment-friendly,
(iii) synthetic procedure should provide high yields regard-
less of nature of substituent(s) on aliphatic or aromatic
compound, (iv) synthetic protocol should have feature of
selectivity, (v) synthetic approach must be applicable for
electron-donating as well as for electron-withdrawing sub-
stituents, and (vi) synthetic methodology must be capable to
avoid over-oxidation. It is implications for synthetic chemist
to design and develop such transformational strategies which
fulfill all these requirements.
For future research, authors of the review have made
a number of suggestions and recommendations. The fol-
lowing are these implications: (i) in some transformational
strategies, only the synthesis of aldehydes is performed.

13

These approaches must be examined for their effective-
ness toward synthesis of ketones, and (ii) dialdehydes,
trialdehydes and diketones are very important precur-
sors. These precursors are very useful for synthesis of
important symmetrical compounds such as symmetrical
hole transport materials (HTMs) for OLEDs, DSSC and
perovskites. Hence, each transformational strategy must
be investigated for synthesis of dialdehydes, trialdehydes
and diketones, and (iii) identically, aliphatic aldehydes and
ketones are very important compounds; hence, synthetic
chemists must focus on developing and investigating such
protocols that are applicable for synthesis of aliphatic car-
bonyl moieties. Moreover, in some transformational strat-
egies, only synthesis of aromatic aldehydes and ketones
was performed. These approaches must be examined for
synthesis of aliphatic aldehydes and ketones, and (iv)
heterocyclic entities have a wide range of applications.
Transformational strategies must be applied for synthe-
sis of carbonyl-containing heterocyclic compounds. For
example, there is need to investigate the synthesis picoli-
naldehyde, thiophene-2-carbaldehyde, furan-2-carbalde-
hyde, 1H-pyrrole-2-carbaldehyde from 2-(bromomethyl)
pyridine, 2-(bromomethyl)thiophene, 2-(bromomethyl)
furan and 2-(bromomethyl)-1H-pyrrole, respectively, and
(v) investigation for transformation of iodine and fluo-
rine containing halide to aldehydes and ketones is also
required. We hope that these all implications will increase
the scope of transformational strategies.
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0529f
Affiliations
Muhammad Faisal1 · Aamer Saeed1 · Danish Shahzad1,2 · Parsa Dar1 · Fayaz Ali Larik1
 Muhammad
Faisal
mfaisal4646@gmail.com
 Aamer Saeed
aamersaeed@yahoo.com
 Danish Shahzad
d.shahzad@fz-juelich.de
13
Molecular Diversity
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quinones. J Chem Res Part Synop. https://doi.org/10.1039/a9055
98c
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mun. https://doi.org/10.1039/C39900001219
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
1
Department of Chemistry, Quaid-i-Azam University,
Islamabad 45320, Pakistan
2
Institute of Inorganic Chemistry, RWTH Aachen University,
Templergraben 55, 52062 Aachen, Germany