Mild and efficient chemoselective synthesis of acetals and geminal diacetates (acylals) from aldehydes using lanthanum(III) nitrate hexahydrate

Article abstract of DOI:10.1080/00397910801986010

A mild and efficient chemoselective method has been developed for the preparation of acetals and gem-diacetates in good to excellent yields through a reaction of aldehydes with ethlyleneglycol or acetic anhydride using catalytic amounts of lanthanum(III) nitrate hexahydrate as a catalyst under solvent-free conditions. Copyright Taylor & Francis Group, LLC.

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Mild and Efficient Chemoselective Synthesis
of Acetals and Geminal Diacetates (Acylals)
from Aldehydes using Lanthanum(III) Nitrate
Hexahydrate
M. Srinivasulu a , N. Suryakiran a , K. Rajesh a , S. Malla Reddy a & Y.
Venkateswarlu a
a Natural Products Laboratory, Organic Chemistry Division I , Indian Institute
of Chemical Technology , Hyderabad, India
Published online: 09 May 2008.
To cite this article: M. Srinivasulu , N. Suryakiran , K. Rajesh , S. Malla Reddy & Y. Venkateswarlu (2008)
Mild and Efficient Chemoselective Synthesis of Acetals and Geminal Diacetates (Acylals) from Aldehydes
using Lanthanum(III) Nitrate Hexahydrate, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 38:11, 1753-1759, DOI: 10.1080/00397910801986010
To link to this article: http://dx.doi.org/10.1080/00397910801986010
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Synthetic Communicationsw, 38: 1753–1759, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801986010
Mild and Efficient Chemoselective Synthesis
of Acetals and Geminal Diacetates (Acylals)
from Aldehydes using Lanthanum(III)
Nitrate Hexahydrate
M. Srinivasulu, N. Suryakiran, K. Rajesh, S. Malla Reddy,
and Y. Venkateswarlu
Natural Products Laboratory, Organic Chemistry Division I, Indian
Institute of Chemical Technology, Hyderabad, India
Abstract: A mild and efficient chemoselective method has been developed for the prep-
aration of acetals and gem-diacetates in good to excellent yields through a reaction of
aldehydes with ethlyleneglycol or acetic anhydride using catalytic amounts of lantha-
num(III) nitrate hexahydrate as a catalyst under solvent-free conditions.
Keywords: Acetals, aldehydes, gem-diacetates, lanthanum(III) nitrate hexahydrate
INTRODUCTION
Selective protection and deprotection of carbonyl compounds plays an
important role in the multistep organic synthesis of complex natural
products. Acetals are among the most popular protecting groups for carbonyl
compounds.[1] Acetals, as a functional group that is stable under neutral and
basic conditions, are not only the most widely used protecting groups but are
also efficient chiral auxiliary groups for enantioselective synthesis.[2]
Numerous procedures have described the formation of acetals under acidic con-
ditions. These include different acid catalysts such as SbCl3;[3] WCl6;[4]
ZrCl4;[5] PTSA;[6] InCl3;[7] FeCl3;[8] I2;[9] CAN;[10] ZnCl2;[11] anhydrous
Address correspondence to Y. Venkateswarlu, Natural Products Laboratory,
Organic Chemistry Division I, Indian Institute of Chemical Technology, Hyderabad
5000 07, India. E-mail: luchem@iict.res.in
1753

1754
M. Srinivasulu et al.
ferroussulphate;[12] triflates;[13] oxidizing agents such as NBS,[14] SeO2,[15] and
DDQ;[16] and solid-supported reagents such as silica-bound H2SO4
and
[17]
silica-supported perchloric acid.[18] However, several of these reported
methods are associated with drawbacks involving low chemo selectivity,
incompatibility with other protecting groups, strong acidic conditions, long
reaction times, and tedious procedure for the preparation of catalyst, and
most of the methods demand dry reaction media. All the Lewis acids require
dry media and large amounts of reagent if the substrate contains nitrogen, as
Lewis acids are trapped by the nitrogen. Thus there is a need for suitable,
mild, and selective alternative for the synthesis of acetals.
.
Recently, we reported La(NO3)3 6H2O as a mild and efficient catalyst
for various organic transformations[19] such as chemoselective deprotection
of primary acetonides; tetrahydropyranylation of primary alcohols; acety-
lation of alcohols, phenols, and amines; mild and efficient Ntert-butoxycabo-
nylation; and N-bezoyloxycarbonylation of amines; synthesis of a-amino
nitriles, 4(3H)-quinazolinones, and benzodiazepines. In the course of study
of these reactions, it has been observed that the substrates containing other
acid labile functional groups such as tert-butyldimethylsilyl (TBDMS)
ethers, some isopropylidene protected diols, and Ntert-Boc protected amines
.
were intact in the presence of La(NO3)3 6H2O. In continuation of our work
using mild and efficient chemoselective Levis acid catalyst in the multistep
synthesis of the natural product, we envisaged the synthesis of acetals and
.
acylals in the presence of a catalytic amount of La(NO3)3 6H2O under
solvent-free conditions.
RESULTS AND DISCUSSION
In this article, we have described an efficient chemoselective method for the
synthesis of acetals and acylals (Schemes 1 and 2) using catalytic amounts
of commercially available inexpensive lanthanum(III) nitrate hexahydrate
under solvent-free conditions. This method does not require expensive
reagents or special care to exclude moisture from the reaction medium.
Initially, we have reacted benzaldehyde with ethylene glycol in the resence
of catalytic amounts (5 mol%) of lanthanum nitrate hexahydrate to yield cor-
responding acetal in excellent yields (90%) at room temperature under
solvent-free conditions. Encouraged by the results obtained for the protection
of aldehydes as their corresponding acetals, we turned our attention to another
important protection of aldehydes as their geminal acetates (acylals). Acylals
Scheme 1.

Acetals and Geminal Diacetates
1755
Scheme 2.
are also one of the useful protecting groups for carbonyls compounds because
of their stability under neutral and basic media as well as aqueous acids.[20]
Moreover, the diacetates of a,b-unsaturated aldehydes serve as an
important precursors for Diels–Alder reactions, and some industrial uses of
these compounds also have been reported.[21,22] Usually the acylals are
prepared from the reaction of aldehydes and acetic anhydride using strong
protic acids or Lewis acids, which include H2SO4, triflicacid, PCl3, ZnCl2,
.
FeCl3, I2, Sc(OTf)3, Cu(OTf)2, Bi(OTf)3 xH2O, AlPN12O40, and Zn(BF4)2.
The successes of the two reactions led us to test the veracity of the method
on various substrates to give corresponding acetals (Scheme 1, Table 1) and
acylals (Scheme 2, Table 2) in excellent yields respectively.
It is also evident from Tables 1 and 2 that a large number of acid-sensitive
groups remain intact during the protection as acetals and acylals. Only
Table 1. Protection of aldehydes as acetals using lanthanum(III) nitrate hexahydrate
as a catalyst under solvent-free conditions
Entry
Substrate
Producta
Time (h)
Yield (%)b
1
2
3
4
5
6
R ¼ H
1a
1b
1c
1d
1e
1f
1.5
1.2
1.4
2
90
92
86
84
90
92
R ¼ Me
R ¼ Cl
R ¼ NO2
R ¼ Ome
R ¼ OTBDMS
1.5
1.2
7
8
R ¼ Bn
R ¼ Bz
2a
2b
3a
1.5
1.5
1
80
82
95
9
4a
1.2
92
1
aAll compounds were characterized by H NMR and EIMS spectral data.
bIsolated yields after column chromatography.

1756
M. Srinivasulu et al.
Table 2. Protection of aldehydes as geminal acetates using lanthanum(III) nitrate
hexahydrate as a catalyst under solvent free conditions
Entry
Substrate
Producta
Time (h)
Yield (%)b
1
2
3
4
5
R ¼ TBDMS
R ¼ Bz
1a
1b
1c
1d
1e
2
2.5
2
92
86
90
92
90
R ¼ Bn
R ¼ Me
R ¼ Ac
2.5
2
6
7
8
9
R ¼ Bn
R ¼ Bz
R ¼ Ac
R ¼ Me
2a
2b
2c
2d
3
3
85
82
90
92
3.5
3
10
11
12
13
14
15
16
17
18
19
R ¼ H
3a
3b
3c
3d
3e
3f
2
2.5
2.5
3
95
92
86
90
92
86
88
90
80
80
85
R ¼ Me
R ¼ Cl
R ¼ NO2
R ¼ OMe
3
R ¼ OTBDMS
R ¼ OTHP
R ¼ OCH2CH55CH2
R ¼ O-Propargyl
R ¼ O-Prenyl
2
3g
3h
3i
2.5
3
3
3j
4a
2.5
2.5
20
21
22
5a
6a
7a
2
2.5
2
88
86
92
23
24
Benzophenone
Acetophenone
—
—
24
24
No product
No product
1
aAll compounds were characterized by H NMR and EIMS spectral data.
bIsolated yields after column chromatography.

Acetals and Geminal Diacetates
1757
aldehydes underwent protection as acetals and acylals under these reaction
conditions, whereas ketones were not protected in similar reaction conditions
even after 24 h (Table 2, entries 8 and 9).
CONCLUSION
In conclusion, we have developed a mild and efficient reagent, lanthanum(III)
nitrate hexahydrate, for protection of aldehydes as acetals and acylals using
ethylene glycol and acetic anhydride under solvent-free condition at room
temperature. The reaction conditions do not require dry conditions.
EXPERIMENTAL SECTION
Typical Experimental Procedure
.
Finely powdered La(NO3)3 6H2O (5 mol%) was added to a mixture of
aldehyde (1 mmol) and acetic anhydride (2.2 mmol) or ethylene glycol
(1.1 mmol), and the reaction was stirred under solvent-free conditions at
room temperature for an appropriate time (Tables 1 and 2). After completion
of the reaction as monitored by thin-layer chromatography (TLC), water
(10 mL) was added to the reaction mixture, and the product was extracted
into ethyl acetate (3 Â 20 mL). The combined organic layer was washed
with brine solution, dried over anhydrous sodium sulphate, and concentrated
under reduced pressure to give the crude product, which was purified over a
silica-gel column to afford corresponding acylals or acetals respectively.
ACKNOWLEDGMENTS
The authors are thankful to Council of Scientific and Industrial Research
(CSIR), Ministry of Earth Sciences (MoES), and Department of Biotechnol-
ogy (DBT), New Delhi, India, for the financial support and to J. S. Yadav,
director, Indian Institute of Chemical Technology (IICT), for his
encouragement.
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