On-column solvent-free oxidative cleavage reactions of vicinal diols by silica gel and paraperiodic acid: Application to in-situ sequential oxidation and Knoevenagel reactions

Article abstract of DOI:10.1002/ejoc.201101329

An on-column solvent-free oxidative cleavage reaction of vicinal diols by paraperiodic acid supported on silica gel at room temperature is described. The resulting pure carbonyl compounds are prepared in good to excellent yields with short reaction times. The cleavage reactions proceed under mild conditions, which avoids further cyclization reactions of the product dialdehydes. This method is also used for sequential oxidation and Knoevenagel reactions to prepare condensation products in good yields by using paraperiodic acid on a mixed bed of alumina and silica gel. The on-column solvent-free oxidative cleavage reaction of vicinal diols by paraperiodic acid supported on silica gel at room temperature is investigated. This approach is applied to an oxidation andKnoevenagel reaction sequence by using a mixed bed of alumina and silica gel to give condensation products in good yields. Copyright

Full text of DOI:10.1002/ejoc.201101329

FULL PAPER
DOI: 10.1002/ejoc.201101329
On-Column Solvent-Free Oxidative Cleavage Reactions of Vicinal Diols by
Silica Gel and Paraperiodic Acid: Application to In-Situ Sequential Oxidation
and Knoevenagel Reactions
[a]
[a]
[a]
Saada C. Dakdouki, Didier Villemin,* and Nathalie Bar
Keywords: Reactive chromatography / Cleavage reactions / Oxidation / Solid-phase synthesis / Domino reactions
An on-column solvent-free oxidative cleavage reaction of
vicinal diols by paraperiodic acid supported on silica gel at
room temperature is described. The resulting pure carbonyl
compounds are prepared in good to excellent yields with
short reaction times. The cleavage reactions proceed under
mild conditions, which avoids further cyclization reactions of
the product dialdehydes. This method is also used for se-
quential oxidation and Knoevenagel reactions to prepare
condensation products in good yields by using paraperiodic
acid on a mixed bed of alumina and silica gel.
Introduction
tions of the resulting dialdehydes, but this could be avoided
by carrying out the scission reactions under milder condi-
tions, at room temperature, and in the presence of minimal
volumes of solvent. Here we report a new on-column oxi-
The development and invention of new synthetic strate-
gies and technologies represent major challenges for organic
chemists, and different innovative methodologies have been
developed to increase synthetic efficiency. One such ap-
proach is the on-column strategy.[1] In our ongoing research
into reactive chromatography, we are interested in ex-
tending the application of our methodology to various
chemical reactions (Horner–Emmons, Wittig, oxidative
cleavage reaction of vicinal diols) as well as to new reaction
dation of vicinal diols by using silica gel supported H IO6
5
at room temperature under solvent-free conditions.
Results and Discussion
Choice of Inorganic Support
[
2]
sequences.
Three different inorganic supports – montmorillonite
The oxidative carbon–carbon bond cleavage of 1,2-diols
K10, alumina, and silica gel – along with solid H IO as an
has been extensively investigated. Various reagents have
5
6
been used for this transformation;[3] periodic acid (H IO )
oxidant, were tested for the on-column oxidative cleavage
reaction of cis-1,2-diphenylethane-1,2-diol (1). The diol, in-
5
6
[
4]
and its salts were first employed by Malaprade in 1928.
Oxidative cleavage reactions with H IO can be performed
organic support, and H IO were ground together. The re-
5
6
5
6
sulting fine powder was packed in a solid-phase extraction
(SPE) column in which the oxidation reaction was allowed
to proceed at room temperature (Figure 1).
in either water or aprotic organic solvents such as diethyl
ether or tetrahydrofuran.[ Although H IO is a strong oxi-
5]
5
6
dant and one of the classical oxidants for the cleavage reac-
tions of vicinal diols, few examples of its use as a supported
reagent have been reported. Villemin and co-workers em-
ployed alumina-supported H IO in the presence of transi-
5
6
tion metal complexes or salts to oxidize α-phenyl olefins to
aldehydes in carbon tetrachloride.[ Previously, we de-
scribed the efficient on-column oxidative cleavage reaction
6]
of vicinal diols by using alumina-supported KIO under mi-
4
crowave irradiation in the absence of solvent.[ These ex-
2b]
perimental conditions led to intramolecular aldol cycliza-
Figure 1. On-column oxidative cleavage reaction of vicinal diols by
5 6
H IO and various inorganic supports.
[
a] Laboratoire de Chimie Moléculaire et Thioorganique,
UMR CNRS 6507, INC3M, FR 3038,
Surprisingly, the use of montmorillonite K10 as the inor-
ganic support with H IO led to a violent and exothermic
ENSICAEN & Université de Caen,
1
4050 Caen, France
5
6
Fax: +33-2-31452877
reaction that gave off characteristic violet fumes of iodine
within a few seconds. Alumina underwent acidic/basic in-
teractions with H IO that resulted in the break down of
E-mail: didier.villemin@ensicaen.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101329.
5
6
780
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 780–784

On-Column Solvent-Free Oxidative Cleavage Reactions of Vicinal Diols
Table 1. Optimization of the on-column oxidative cleavage reaction the solid support and liberation of water. Pleasingly, the
5 6
of vicinal diols by H IO for various inorganic supports.
oxidation reaction of cis-1,2-diphenylethane-1,2-diol by sil-
ica gel and H IO occurred smoothly to afford benzalde-
5
6
hyde (2) in 99% yield (Table 1). On the basis of these results,
silica gel was chosen as the inorganic support for the cleav-
age reactions.
On-Column Oxidative Cleavage by Silica Gel and H IO6
5
We used a supported-reagent on-column approach to in-
vestigate the oxidation of several vicinal diols. A finely
ground mixture of diol, silica gel, and H IO was loaded
5
6
onto a SPE column and afforded pure aldehydes in 15–
5 6
Table 2. On-column oxidative cleavage reaction of vicinal diols by silica gel supported H IO under solvent-free conditions.
Eur. J. Org. Chem. 2012, 780–784
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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781

S. C. Dakdouki, D. Villemin, N. Bar
Table 3. On-column sequential oxidative cleavage and Knoevenagel reactions by using a mixed bed of alumina and silica gel supported H IO
FULL PAPER
5
6
.
1
[
a] Yield determined by H NMR spectroscopy. [b] Yield determined by GC–MS.
782
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Eur. J. Org. Chem. 2012, 780–784

On-Column Solvent-Free Oxidative Cleavage Reactions of Vicinal Diols
6
0 min at room temperature in good to excellent yields. No and co-workers.[10] The Knoevenagel condensation with
solvent was required. This approach permitted efficient and Meldrum’s acid (28) gave desired product 29 in 30 min in
smooth cleavage of both substituted α,αЈ-diphenylethane- only 28% yield (Table 3, Entry 9). The reaction of 28 with
1
,2-diols and cycloalkane-1,2-diols. The oxidative cleavage 15 and 17 was reported by Villemin with the use of neutral
[
11]
reaction of various diols is summarized in Table 2. For ex- alumina at room temperature in 5 h.
ample, 1,2-bis(4-methoxyphenyl)ethane-1,2-diol (3), 1,2-
The Henry reaction was also investigated by using nitro-
bis(3,4-dioxymethyleneyphenyl)ethane-1,2-diol (5), and 1,2- methane (25) as the acidic compound (Table 3, Entry 8).
bis(3,4,5-trimethoxyphenyl)ethane-1,2-diol (7) gave 4-meth- In this case, cis-1,2-diphenylethane-1,2-diol (1) is cleaved to
oxybenzaldehyde (4), piperonal (6), and 3,4,5-trimethoxy- form benzaldehyde (2), which immediately condenses with
benzaldehyde (8) in 99, 70, and 91% yield, respectively nitromethane to yield nitrostyrene derivative 26. This com-
(Table 2, Entries 2–4). Similarly, cis-cyclohexane-1,2-diol pound then undergoes a Michael reaction with another ni-
(9), 3,7,7-trimethylbicyclo[4.1.0]heptane-3,4-diol (11), and tromethane molecule to give the corresponding Michael ad-
cis-cyclooctane-1,2-diol (13) yielded adipaldehyde (10), 2- duct 27. After 3 h, 88% of the formed aldehyde is converted
2,2-dimethyl)-3-(2-oxopropyl)acetaldehyde (12), and oc- affording a mixture of β-nitrostyrene (26) and Michael ad-
(
tanedial (14) in 77, 96, and 83% yield, respectively (Table 2, duct 27 in 44 and 27% yield, respectively (determined by
Entries 5–7). Interestingly, this system enables easy oxidat- GC–MS).
ive cleavage of α,αЈ-diphenylethane-1,2-diols (i.e., 1, 3, 5,
and 7) at room temperature, unlike the cleavage reactions
with alumina and KIO that necessitate the use of micro- Conclusions
4
[
2b]
wave irradiation.
Furthermore, the silica gel/H IO sys-
5 6
We have developed a rapid, simple, and efficient pro-
cedure for the on-column oxidative cleavage reaction of
vicinal diols in the solid state by using silica gel and H IO .
tem permitted smooth cleavage of cycloalkane-1,2-diols, in
the absence of solvent, to give the corresponding dialde-
hydes without further intramolecular aldol cyclization reac-
tion.
5
6
This protocol does not require pre-preparation of the sup-
ported oxidant or dissolution of H IO or the diol. The
5
6
scission reactions proceed without the need for toxic, vola-
tile organic solvents or aqueous workups. This method al-
lows easy cleavage of substituted 1,2-diphenylethane-1,2-di-
ols and cycloalkane-1,2-diols with short reaction times un-
der mild conditions. This methodology can also be em-
ployed for on-column sequential oxidation and Knoevena-
gel reactions by using a mixed bed of alumina and silica
gel and H IO permitting the successful formation of the
Sequential Oxidative Cleavage and Knoevenagel Reaction
by using Supported H IO over a Mixed Bed of Alumina
and Silica Gel
5
6
The on-column oxidation and Knoevenagel reaction se-
quence was studied by using a mixed bed of alumina and
silica gel with H IO . The SPE columns were loaded with
5
6
5
6
condensation products at room temperature and in good
yields. These results open the door for investigation of other
reaction sequences.
a mixture of alumina and silica gel with H IO (prepared
5
6
as described previously, Figure 1). A solution of the diol
and acidic methylene compound was then adsorbed on the
mixed bed and the cleavage reactions were allowed to pro-
ceed at room temperature. The reaction products were col-
lected by simple elution with dichloromethane. The choice
of the eluent was important because H IO is soluble in
Experimental Section
5
6
General Methods: All commercial reagents were purchased from
Acros, Aldrich, and Sigma and were used as received. Reaction
no interaction between the alumina and the silica gel/H IO6 times were monitored by using TLC until no starting material re-
more polar solvents such as tetrahydrofuran. We note that
5
mixture was observed.
254
mained. TLC was performed by using Silica gel 60 F precoated
1
13
The oxidation and Knoevenagel reaction sequence was aluminum sheets. H and C NMR spectra were recorded with a
Bruker AC 250 or Bruker AC 400 spectrometer. Chemical shifts (δ)
investigated with several diols and acidic methylene com-
were referenced to the internal deuterated solvents with tetrameth-
pounds. The oxidative cleavage reactions occurred smoothly
ylsilane as the internal standard. Mass spectra were recorded with
with complete conversion of the starting diols. The Knoev-
a QTOF Micro (Waters) spectrometer with electrospray ionization
enagel step took place with 80–95% conversion. Thus, the
mixed bed of alumina and silica gel mixed with H IO per-
mitted the preparation of a number of Knoevenagel prod-
ucts in 30–180 min in moderate to good yields, as shown in
Table 3. Malononitrile (15) and diethyl cyanoacetate (17) with those reported in the literature. References are cited either in
(
ESI, positive mode), lockspray orthophosphoric acid, infusion in-
5
6
troduction at 10 μL/min, a source temperature of 80 °C and desol-
vation temperature of 120 °C. All the compounds synthesized in
this work are known and their spectroscopic data are in agreement
reacted efficiently with the formed aldehydes affording the the text or in the tables.
condensation products in good yields (Table 3, Entries 1, 2,
Preparation of Substituted 1,2-Diphenylethan-1,2-diols 3, 5, and 7:
4–7). Diethylmalonate (19) did not react at all with benzal-
These diols were prepared as mixtures of cis and trans isomers
dehyde (2) under these conditions. Such non-reactivity of
[21]
through a pinacol coupling described by Zhang and Li. The mix-
diethylmalonate with aldehydes in the presence of alumina tures of isomers were subjected to glycolic cleavage without separa-
at room temperature has been reported by Texier-Boullet tion.
Eur. J. Org. Chem. 2012, 780–784
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783

S. C. Dakdouki, D. Villemin, N. Bar
FULL PAPER
General Procedure for the On-Column Oxidative Cleavage Reaction [3] a) E. Baer, J. M. Grosheintz, H. O. L. Fischer, J. Am. Chem.
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of Vicinal Diols by using Silica Gel Supported H
5 6
IO Acid: A mix-
1
ture of diol (1 mmol), silica gel (1 g), and H IO (1.5 g) was ground
5
6
D. H. R. Barton, J. P. Kitchin, D. J. Lester, W. B. Motherwell,
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the solvent in vacuo afforded the corresponding scission products.
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Knoevenagel Reactions by using a Mixed Bed of Alumina, and Silica
gel, and H IO : A mixture of H IO (0.75 g) and silica gel (0.5 g)
5 6 5 6
was ground together before being mixed well with alumina (3.0 g)
and loaded onto a SPE column (Varian Bond Elut, 6 mL) equipped
with a frit at the lower end. A solution of the diol (0.5 mmol) and
the acidic methylene compound (1 mmol) in dichloromethane
(
0.2 mL) was adsorbed on the support in the SPE column. The
reaction was allowed to proceed at room temperature for 30–
80 min. The reaction product was then eluted from the column
2
1
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de la Recherche Scientifique, the Région Basse-Normandie, and
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Received: September 11, 2011
Published Online: December 1, 2011
Org. Chem. 2011, 4448–4454.
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