Chemoselective protection of aldehydes in the presence of ketones using rupvp complex as a heterogeneous catalyst

Article abstract of DOI:10.1080/00397910902985457

Ruthenium(III)-polyvinyl pyridine (RuPVP) complex was prepared by refluxing a methanolic solution of polyvinyl pyridine and trihydrated ruthenium trichloride. RuPVP catalyst was characterized by Fourier transform-infrared and diffential scanning calorimetry-thermogravimetry (TG). The catalyst was used for chemoselective protection of aldehydes in the presence of a ketonic carbonyl group.

Full text of DOI:10.1080/00397910902985457

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Chemoselective Protection of Aldehydes
in the Presence of Ketones Using RuPVP
Complex as a Heterogeneous Catalyst
a
a
a
Siddheshwar W. Kshirsagar , Nitin R. Patil & Shriniwas D. Samant
a
Organic Chemistry Research Laboratory , University Institute of
Chemical Technology , Matunga, Mumbai, India
Published online: 06 Jan 2010.
To cite this article: Siddheshwar W. Kshirsagar , Nitin R. Patil & Shriniwas D. Samant (2010)
Chemoselective Protection of Aldehydes in the Presence of Ketones Using RuPVP Complex
as a Heterogeneous Catalyst, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:3, 407-413, DOI: 10.1080/00397910902985457
To link to this article: http://dx.doi.org/10.1080/00397910902985457
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Synthetic Communications , 40: 407–413, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902985457
CHEMOSELECTIVE PROTECTION OF ALDEHYDES
IN THE PRESENCE OF KETONES USING RuPVP
COMPLEX AS A HETEROGENEOUS CATALYST
Siddheshwar W. Kshirsagar, Nitin R. Patil,
and Shriniwas D. Samant
Organic Chemistry Research Laboratory, University Institute of Chemical
Technology, Matunga, Mumbai, India
Ruthenium(III)-polyvinyl pyridine (RuPVP) complex was prepared by refluxing a
methanolic solution of polyvinyl pyridine and trihydrated ruthenium trichloride. RuPVP
catalyst was characterized by Fourier transform–infrared and diffential scanning
calorimetry–thermogravimetry (TG). The catalyst was used for chemoselective protection
of aldehydes in the presence of a ketonic carbonyl group.
Keywords: Heterogeneous catalysts; polyvinyl pyridine; protection
INTRODUCTION
Protection of functional groups is a crucial step in many multistep syntheses.
Often a carbonyl group needs a protection–deprotection step. A carbonyl group
can be protected by converting it into acetals, dioxolanes, diacetates, thiacetals, or
[1]
oxathiolanes. The critical issue in the protection of a carbonyl group is the chemos-
electivity when more than one carbonyl group is present in the substrate (e.g.,
protection of aldehyde group in an oxoaldehyde). Protection of the aldehyde
function is an important step in the synthesis of drugs; therefore, there is a demand
for chemoselective protection of the aldehyde function in the presence of a ketonic
carbonyl group. The protection of aldehydes is done by using alcohols, diols, thiols
or dithiols, trialkylorthoformate, and so on.
Acetalization is one of the most widely used methods for protection of
[2]
aldehydes and ketones. Acetals are stable in an alkaline medium and decompose
in an acidic medium. Acetals are not only important as protected carbonyl com-
pounds, but many acetals find applications as flavors and perfumery compounds.
Different acetals have characteristic odors. For example, benzene dimethyl acetal
(2a) is occasionally used in perfumes and in flavor compositions for imitation of
Received January 31, 2009.
Address correspondence to Shriniwas D. Samant, Organic Chemistry Research Laboratory,
University Institute of Chemical Technology, N. M. Parekh Marg, Matunga, Mumbai 400 019, India.
E-mail: samantsd@yahoo.com
4
07

408
S. W. KSHIRSAGAR, N. R. PATIL, AND S. D. SAMANT
cherry, fruit, nut, or almond. 2-Phenyl-1,3-dioxolane is used in flavor compositions
where storage conditions favor a more stable form of benzaldehyde. Citral dimethyl
acetal is used in soap. Heptanal dimethyl acetal (2h) can be used as a flavoring agent.
From the previous literature, we noticed that different metal salts have been
[
3]
[4]
[5]
used for the acetalization of carbonyl compounds (e.g., LaCl , TiCl4, ZrCl4,
3
[
6]
[7]
[8]
InCl3, CeCl3, Sc(OTf)3, FeCl ). In some methods, the aldehyde protection
[9]
3
10]
[
[11]
[12]
[13]
has been carried out using HCl,
[15]
NHOH, DDQ, and DCC-SnCl4.
PTSA,
[16]
TMSOTf,
TMSOFs,
PHSO2
[
14]
Heterogeneous catalysts often have advantages over classical catalysts because
of their unique properties such as reusability, ease of handling, and environmental
friendliness. Several heterogeneous catalysts such as zeolites (Y-zeolite, Y-zeolite
[
17]
HSZ-360, ZSM-5, delaminated zeolite ITQ-2), cation-exchanged montmorillonite
[20]
nþ
3þ
4þ
3þ
3þ
21]
þ
2þ [18]
[22]
[19]
(M
tetramethlysilane (TMS),
¼ Ce , Ti , Fe , Al , Na , Zn ),
mont. KSF,
SiO =H SO ,
2 2 4
alumina,
nafion=
[24]
SiO =NaHSO ,
[
[23]
HBF -SiO ,
4
2
2
4
[
25]
2ꢀ [26]
[27]
[28]
AIPO =Al O ,
4
ZrO =SO4
2
,
Pt=MoO =ZrO ,
3
Envirocat EPZG,
and
2
29]
3
2
[
MCM-41 have been used for acetalization of carbonyl compounds. However, very
few methods have been reported for chemoselective protection of aldehydes in the
presence of ketones. De and Gibbs have reported the acetalization of aldehydes in
[
30]
the presence of RuCl ꢁ 3H O under reflux condition,
whereas Qi et al. have
The latter method has many
3
2
[
31]
attempted the same reaction at room temperature.
advantages such as high chemoselectivity, low loading of catalyst, and mild reaction
conditions. However, the method has one disadvantage; anhydrous sodium sulfate is
needed in the reaction to remove the water generated.
We recently reported polyvinyl pyridine (PVP) as a heterogeneous basic
[
32]
catalyst. Preparation of PVP complexes of transition-metal ions is possible by
reacting PVP with metal halides in refluxing methanol. One of such complexes is
[
33]
ruthenium(III)–PVP, reported by Clear et al.
Inspired by the successful use of
ruthenium trichloride in the acetalization reaction, we used RuPVP in the chemose-
lective protection of aldehydes in the presence of ketones.
We prepared PVP by radical polymerization of vinyl pyridine in the presence
of azobisisobutyronitrile (AIBN). Ruthenium(III)–PVP was prepared as a hetero-
[33]
geneous catalyst by the reported method.
Protection of 4-nitrobenzaldehyde (1b) with methanol in the presence of
RuPVP catalyst was taken as a model reaction to optimize the reaction conditions
(Scheme 1). The reaction did not take place in the absence of a catalyst at room
temperature. To optimize the catalyst amount, the reaction was carried out using dif-
ferent quantities of the catalyst (Table 1). Reaction proceeded well with 3.9 mol% of
the catalyst; with less catalyst, less conversion of the aldehyde was observed. The
reaction was carried out using different alcohols: methanol, ethanol, isopropanol,
Scheme 1. Formation of acetal aldehydes.

SELECTIVE ACETAL FORMATION
409
Table 1. Optimization of the quantity of RuPVP in the reaction of 1b with
methanol
No.
Catalyst quantity (mg, mol%)
Isolated yield of 2b (%)
1
2
3
4
30, 2.35
40, 3.13
50, 3.90
00, 0.00
79
84
92
Trace
Note. Reaction condition: 1b (0.45 g, 3 mmol), methanol (10 ml), 4 h, at
ꢂ
68–70 C.
Table 2. Reaction of 1b with different alcohols in the presence of RuPVP
No.
Alcohol
Isolated yield of 2 (%)
1
2
3
4
Methanol
Ethanol
92
87
54
72
Isopropyl alcohol
Ethylene glycol
Note. Reaction condition: 1b (0.45 g, 3 mmol), alcohol (10 ml), and RuPVP
ꢂ
(
50 mg), 4 h, at 68–70 C.
Table 3. The reusability of RuPVP catalyst in the reaction of 1b with
methanol
No.
Run
Isolated yield of 2b (%)
1
2
3
4
1
2
3
4
92
92
91
88
Note. Reaction condition: 1b (0.45 g, 3 mmol), methanol (10 ml), and
ꢂ
RuPVP (50 mg), 4 h, at 68–70 C.
Scheme 2. Chemoselective formation of acetal benzaldehyde (1b) in the presence of acetophenone (3).

410
S. W. KSHIRSAGAR, N. R. PATIL, AND S. D. SAMANT
Table 4. Acetalization of various aldehydes with methanol in the presence of RuPVP
No.
1
Carbonyl compound
Acetal
Time (h) Isolated yield of 2 (%)
8
4
87
92
2
3
5
87
81
4
3.5
5
6
10
74
56
14
7
8
8
8
65
78
9
10
67
1
1
0
1
24
24
00
00
ꢂ
Note. Reaction condition: Aldehyde (3 mmol), methanol (10 ml), and RuPVP (50 mg) at 68–70 C. The
products were characterized by GC-MS and FT-IR.

SELECTIVE ACETAL FORMATION
411
and ethylene glycol (Table 2). The reaction with methanol was much faster than that
with other alcohols. The RuPVP is a heterogeneous catalyst and could easily be
separated from the reaction mixture by filtration. The recovered catalyst was used
for successive runs to test its reusability (Table 3).
To check the chemoselectivity, we carried out reaction of an equimolar mixture
of 4-nitrobenzaldehyde (1b) and 4-nitroacetophenone (3) with methanol in the pres-
ence of RuPVP (Scheme 2). It was found that only 4-nitrobenzaldehyde underwent
protection, and 4-nitroacetophenone remained completely unreacted.
Under the optimized conditions, a series of aldehydes was reacted with meth-
anol to form the corresponding acetals (Table 4). The reaction of ketonic carbonyl
group with methanol in the presence of RuPVP did not take place (entries 10 and 11).
In earlier reported methods, there are some disadvantages such as use of
trialkyl-orthoformate as a protecting group, harsh reaction conditions (e.g., strong
acids), use of classical metal catalysts, and poor selectivity. Herein, we are reporting
Ru-PVP as a heterogeneous catalyst for chemoselective protection of aldehydes in
the presence of ketones. In conclusion, we can say that the procedure is green and
environmentally benign.
EXPERIMENTAL
PVP was prepared by radical polymerization of 4-vinylpyridine according to
the reported method.
Preparation of Ru(III) Complex with Polyvinyl Pyridine
A solution of RuCl ꢁ 3H O (212.4 mg, 0.87 mmol) in methanol (10 ml) was
3
2
added dropwise to a solution of PVP (166.5 mg) in methanol (50 ml). The solution
was refluxed for 45 min and cooled. The brown precipitate was filtered by suction,
washed with methanol (3 ꢃ 5 ml), and dried under vacuum.
Typical Reaction Procedure
To a 100-ml, round-bottom flask, aldehyde (3 mmol), methanol (10 ml), and
ꢂ
Ru-PVP (0.05 g) were added. The solution was refluxed (68–70 C) until the aldehyde
was consumed (thin-layer chromatography). The reaction mixture was allowed to
cool to room temperature and filtered, and the catalysts were washed with methanol
(
3 ꢃ 10 ml). The filtrate was dried over anhydrous Na SO and concentrated under
2
4
reduced pressure. The product was purified by column chromatography on silica
gel (60–120 mesh) with eluent [EtOAc–pet. ether (60–80) ¼ 6:94]. For the compounds
2
b, 2c, and 2d, no purification was needed as they were obtained in pure form.
ACKNOWLEDGMENT
The authors thank the Council of Scientific and Industrial Research, New
Delhi, for Research Grant No. 01 (2056)=06=EMR-II.

412
S. W. KSHIRSAGAR, N. R. PATIL, AND S. D. SAMANT
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