(±)-Camphor sulfonic acid assisted IBX based oxidation of 1° and 2° alcohols

Full text of DOI:10.1016/j.tetlet.2021.153298

Tetrahedron Letters xxx (xxxx) xxx
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( )-Camphor sulfonic acid assisted IBX based oxidation of 1° and 2°
alcohols
Kamlesh Kumar a,b, Penny Joshi b, Diwan S Rawat a,
⇑
a Department of Chemistry, University of Delhi, Delhi 110007, India
b Department of Chemistry, DSB Campus, Kumaun University, Nainital, Nainital 263601, India
Introduction
Result and discussion
Oxidation of alcohols is a very common reaction in organic
synthesis. Oxidation of alcohol results carbonyl compounds like
aldehyde, ketone, carboxylic acid [1]. Carbonyl compounds are
the key synthons in synthetic organic chemistry i. e., these are
the starting material for the development of drugs, antibiotics
and agrochemicals, ring systems etc. Several efforts have been
made to oxidize alcohols [2].
Optimization of reaction condition
Initially 4-nitrobenzyl alcohol was oxidized using IBX as an oxi-
dant in DCM at room temperature. No isolable product formation
was observed even after 12 hrs. Surprisingly addition of one equiv-
alent of ( )-Camphor sulfonic acid monohydrate leads to the for-
mation of a new spot on the TLC which was relatively less polar
than alcohol. Preliminary investigation (visualization with 2, 4-
DNP solution) indicates the progress in oxidation and this pro-
moted us to establish this methodology. The solvent screening
results indicated that the binary solvent system (DCM:1,4-dioxane
ratio; 1:1) was the most appropriate solvent for this reaction. Fur-
ther we screened the oxidant IBX and ( )-CSA monohydrate and
combination of 1.2 equivalent of IBX with respect to alcohol and
15–20 mol% of ( )-CSA monohydrate (see SI, Tables 1 and 2) was
found to be optimum combination for this conversion. After opti-
mizing the reaction condition, a verity of 1° and 2° alcohols were
screened.
Under optimized reaction condition verity of benzyl alcohols
(Fig. 1) were oxidized. The oxidation of nitro substituted benzyl
alcohols shows that the 4-nitro benzyl alcohol oxidized faster with
higher yield with respect to 2-nitro benzyl alcohol, it indicates the
retardation of oxidation due to steric effect of nitro group at 2nd
position. The 4-fluoro, 4-chloro and 4-bromo benzyl alcohols were
oxidised and shows almost similar results. The oxidation of 4-
cyano benzyl alcohol was little messy with relatively poor yield.
Piperonal was obtained quickly from the oxidation of piperonyl
alcohol. 4-Methoxy benzyl alcohols were oxidized successfully
with high yield. The oxidation of primary and secondary alcohols,
attached with heterocyclic rings are quite challenging and less
explored with IBX oxidation too. Here in we have oxidised few
such class of alcohols in easy manner.
In recent decade, interest in the hypervalent iodine chemistry
has grown at a rapid pace due to the environmental benign, mild
and highly selective oxidizing nature of these reagents [3,4].
Among these, IBX (o-iodoxybenzoic acid) is one of the fashionable
hypervalent iodine(v) reagent, which may be ascribe to its remark-
able reactivity and commercial availability [4,5]. The insolubility of
IBX in common organic solvents except DMSO, and explosive nat-
ure at high temperature are the main challenges with this reagent
[6]. Since after Dess-Martin periodinane [7], a number of modified
IBXs [8] and solid supported IBX [9] have been prepared to over-
come these problems. However, typical synthetic procedures and
high cost limits the use of these modified IBXs [8]. In contrast, to
avoid the structural modifications and enhance the efficiency of
IBX few additives like oxone [10] acetic acid [11] trifluoroacetic
acid [12] p-toluenesulfonic acid [13] triflic acid or trifluo-
romethanesulfonic acid [14] b-cyclodextrin [15] have been used.
Several reports also demonstrate that IBX is a powerful oxidant
when used in ionic liquids [16] or solvents like EtOAc [17] acetone
or MeCN at elevated temperature [18]. IBX-OTs was reported as a
powerful oxidant in dichloromethane for the oxidation of alcohols.
Recently an IBX based new reagent (IBX-ditriflate) was synthesized
which transform CAH into C-OH (Fig. 1) [14]. In our earlier report
we have used triflic acid in combination with IBX to oxidise alco-
hols but instability of TfOH at room temperature [14], difficult han-
dling and safety concerns compel us to develop more easy and
convenient method for the same. Therefore, herein we have estab-
lished a more convenient methodology.
Different secondary alcohols were successfully oxidized using
( )-camphor sulfonic acid/IBX as catalytic system. The methyl,
hydroxy, and bromo 1-phenylethan-1-ol were oxidised into corre-
sponding acetophenones. The 2,3-dihydro-1H-inden-1-ol was oxi-
dised under these reaction condition with quantitative yield. To
investigate the selectivity in oxidation, the 2,3-dihydro-1H-
indene-1,3-diol was subjected to oxidation under this reaction
condition, the mixed product of 1-indanone and 1,3-indandione
⇑
Corresponding author.
E-mail address: dsrawat@chemistry.du.ac.in (D.S Rawat).
https://doi.org/10.1016/j.tetlet.2021.153298
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Please cite this article as: K. Kumar, P. Joshi and Diwan S Rawat, ( )-Camphor sulfonic acid assisted IBX based oxidation of 1° and 2° alcohols, Tetrahedron
Letters, https://doi.org/10.1016/j.tetlet.2021.153298

K. Kumar, P. Joshi and Diwan S Rawat
Tetrahedron Letters xxx (xxxx) xxx
Fig. 1. IBX based oxidants.
Fig. 2. Oxidation of different primary and secondary alcohols.
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K. Kumar, P. Joshi and Diwan S Rawat
Tetrahedron Letters xxx (xxxx) xxx
Fig. 3. Mass spectrometry of reaction mixture.
Fig. 4. Plausible mechanism of oxidation.
were obtained. This indicates no partial oxidation; the complete
oxidation consumed 2.3 equivalent of IBX with 15 mol% ( )-CSA.
Benzyl allyl alcohol produced chalcone in quantitative yield. Fur-
ther this method was employed to oxidise aliphatic primary and
secondary alcohols (Fig. 2). Sometimes oxidation of the aliphatic
alcohols is more challenging due to poor yield and difficulty in iso-
lation of the products. Few simple alcohols viz cyclopropylethan-1-
ol, 4-methylcyclohexanol, 5-chloropentan-2-one and 6-chloropen-
tan-2-one were oxidised and isolated with high yield. Geraniol was
oxidised into geranial with 79% of isolated yield. The norborneol is
a bulky substrate, which was oxidised successfully with 94% yield.
Admantan-2-one was obtained from the oxidation of adman-
tane-2-ol with a very good yield. The (E)-2-methylbut-2-en-1-ol
was kept under oxidation and isolated yield was 69%. 4-Hydroxy
benzyl alcohol was oxidized under this newly developed method-
ology, the only hydroxy group at benzylic position was oxidised
i.e., 4-hydroxybenzaldehyde was isolated as oxidized product.
The oxidation of trans-menthol in acidic medium may produce
the racemic mixture, so to check the applicability of this method
we have kept the trans-menthol under this oxidation condition
and found that the isolated product was single stereoisomer, which
was confirmed by 1H, 13C and CD spectra (see SI).
benzaldehyde was formed (see SI, 1H NMR, Figs. 1 and 2), while in
case of IBX-( )-CSA based oxidation, 92.3% of 4-nitrobenzaldehyde
was formed. The experiment concludes that the newly develop
methodology is far efficient over oxidation by IBX itself only.
In order to understand the possible cause of trigger in oxidizing
power of IBX in common organic solvent at room temperature, we
performed an experiment and recorded the mass spectrum of the
mixture of IBX and ( )-CSA. The appearance of m/z = 531.1062 in
mass spectrum clearly indicate the formation of C17H24IO9S, which
can be represented best as ‘a’ (Fig. 3).
On the basis of mass spectrum data, the plausible mechanism of
the oxidation is given in Fig. 4. First of all, ( )-CSA monohydrate (2)
reacts with IBX (1) to give a highly reactive oxidant with formula
C17H24IO9S (a) (confirmed by HRMS, see SI). The in-situ generated
oxidant (a) undergoes ligand exchange with alcohol (3) and pro-
duce (4), which undergoes decomposes into carbonyl compound
(5) and IBA (6).
Conclusions
To understand the advantage of IBX-( )-CSA based oxidant in
the oxidation of alcohols, two separate reactions were performed
(a) oxidation of 4-nitrobenzyl alcohol with IBX and (b) oxidation
of 4-nitrobenzyl alcohol with IBX-( )-CSA at room temperature.
1H NMR spectra of both the reaction was recorded. It was found
that the reaction in which the ( )-CSA was not used, 2.6% of 4-nitro
In conclusion, we have developed a practical and efficient
methodology for the oxidation of primary and secondary alcohols
which includes aliphatic, aromatic, heterocycles with differently
substituted functional groups. This method is beneficial in terms
of easy reaction condition, cheap reagents, highly efficient and
quick purification.
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K. Kumar, P. Joshi and Diwan S Rawat
Tetrahedron Letters xxx (xxxx) xxx
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Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
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charged with magnetic bar and 2 mL DCM:1,4-Dioxane. Stirred
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solution of alcohol dropwise for 5 minutes. Stirred the solution at
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the solvent and dilute the reaction mass with DCM. Filter the sus-
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Supplementary data to this article can be found online at
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