Chemoselective protection and deprotection of aldehydes using solid supported reagent (Silica Chloride) under solvent-free conditions

Article abstract of DOI:10.1080/00397911003797866

Silica chloride, a heterogeneous catalyst, has been found to be an efficient catalyst for the protection of aldehydes as acylals under solvent-free conditions, and deprotection of acylals to aldehydes in methanol as a solvent occurred. The reaction takes a shorter time and ensures good to excellent yield of the products.

Full text of DOI:10.1080/00397911003797866

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Chemoselective Protection and
Deprotection of Aldehydes Using Solid
Supported Reagent (Silica Chloride)
Under Solvent-Free Conditions
a
a
Bandita Datta & M. A. Pasha
a
Department of Studies in Chemistry , Bangalore University, Central
College Campus , Bengaluru , India
Published online: 21 Mar 2011.
To cite this article: Bandita Datta & M. A. Pasha (2011) Chemoselective Protection and Deprotection
of Aldehydes Using Solid Supported Reagent (Silica Chloride) Under Solvent-Free Conditions, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:8, 1160-1166, DOI: 10.1080/00397911003797866
To link to this article: http://dx.doi.org/10.1080/00397911003797866
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Synthetic Communications , 41: 1160–1166, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003797866
CHEMOSELECTIVE PROTECTION AND DEPROTECTION
OF ALDEHYDES USING SOLID SUPPORTED REAGENT
SILICA CHLORIDE) UNDER SOLVENT-FREE
(
CONDITIONS
Bandita Datta and M. A. Pasha
Department of Studies in Chemistry, Bangalore University, Central College
Campus, Bengaluru, India
GRAPHICAL ABSTRACT
Abstract Silica chloride, a heterogeneous catalyst, has been found to be an efficient catalyst
for the protection of aldehydes as acylals under solvent-free conditions, and deprotection of
acylals to aldehydes in methanol as a solvent occurred. The reaction takes a shorter time
and ensures good to excellent yield of the products.
Keywords Acylals; aldehydes; deprotection in methanol; heterogeneous catalysis; silica
chloride
INTRODUCTION
[1]
Solid-phase synthesis has become one of the most important tools in organic
synthesis. The solid-phase chemistry concept has recently been used in a much wider
sense to cover both solid-phase substrate and solid-phase reagent chemistry. Sub-
strates are chemically bound to the surface of the solid support and then converted
[
2]
into the product, followed by liberation from the solid under the first approach. In
the second approach, the reagent is bound to the solid support; the solid-phase
[
reagents can be either functionalized organic polymers or silica-gel-grafted cata-
3]
[
lysts. Compared to organic polymers, silica gel is strong enough to withstand harsh
4]
[
5]
conditions. The wide application of solid-supported reagents and catalysts is due to
ease and safety in handling, rate enhancement, good yields, easy workup procedures,
and economy. An inexpensive silica chloride can be prepared easily by treating
[6]
thionyl chloride with silica gel and is a better reagent when compared to thionyl
Received December 29, 2009.
Address correspondence to M. A. Pasha, Department of Studies in Chemistry, Bangalore
University, Central College Campus, Bengaluru, 560001, India. E-mail: m_af_pasha@ymail.com
1
160

PROTECTION/DEPROTECTION OF ALDEHYDES
1161
Scheme 1. Synthesis of silica chloride.
chloride or trimethyl silyl chloride (Scheme 1). Once the reaction gets completed, the
catalyst can be filtered, washed with chloroform, and reused without decrease in
activity for three runs.
In the preparation of many delicate organic compounds, some specific parts of
the molecules cannot survive the required reagents or chemical environments; hence,
[7]
these parts or groups must be protected. The common carbonyl protecting groups
[10]
[
8]
[8]
[9]
are acetals, ketals, acylals, and dithianes.
Acetals and ketals need acids,
dithianes need metal salts or oxidizing agents for deprotection, whereas acylals need
[11]
mild acid catalysts for deprotection. Acylals are very robust to aqueous acid, neu-
tral, and basic media.
Acylals are used as building blocks in the synthesis of dienes required for
Diels–Alder cycloaddition reactions,
cross-linking reagents for cellulose in cotton and serve as activators in the compo-
sition of the bleaching mixture used for the treatment of wire-strained fibers
[
and as substrates in many organic reactions.
[12]
[13]
and acylals have been applied as
[
14]
15]
A wide range of catalysts have been used to convert aldehydes into acylals;
[
16]
17
[18]
[23]
[28]
some of them are LiOTf,
19]
Ceric ammonium nitrate (CAN),
[21]
InCl3,
SbCl3,
[
[20]
[22]
H NSO H,
2
LiBF4,
FeCl3,
H SO ,
2
sulfated zirconia,
N-bromosuccinimide NBS,
[26]
3
4
[24]
[25]
[27]
TMSCl-NaI,
silica sulfuric acid,
Bi(NO ) ,
3 3
[29]
and para-tolunesulfonic acid (p-TSA). Although these are convenient procedures
and give high yields of the desired products, they suffer from one or more drawbacks
such as longer reaction time, highly corrosive nature, they involve expensive cata-
lysts, and use solvents. The deprotection of acylals, on the other hand, has also been
[
21]
[30]
[31]
reported using some of the protic acids such as H SO ,
[
BiCl3,
Most of them are corrosive, expensive, or
Sc(OTf)3,
2
4
17]
[32]
[33]
CAN,
ZrCl4,
and CBr4.
non-reusable catalysts; hence, developing a more efficient, economical, and greener
protocol is still required.
After acknowledging the advantages of solid-supported catalysts, we herein
report the use of silica chloride in the synthesis of 1,1-diacetates by a solvent-free
reaction of araldehydes with acetic anhydride and their deprotection using silica
chloride in the presence of methanol (Scheme 2). Our system takes care of all the
problems encountered with the previously mentioned catalysts.
Scheme 2. Protection and deprotection of aldehydes using acetic anhydride in the presence of silica chloride.

1162
B. DATTA AND M. A. PASHA
Table 1. Conversion of anisaldehyde (1 mmol) to 1,1-diacetoxy-1-(4-methoxyphe-
nyl) methane in the presence of silica chloride in different solvents and under
solvent-free conditions
a
Yield (%)
Entry
Solvent
Time (min)
1
2
3
4
5
THF
DCM
Ether
80
62
60
80
95
20
20
20
20
15
Acetonitrile
Solvent-free reaction
a
Isolated yield.
RESULTS AND DISCUSSION
Synthesis of acylals from aldehydes and acetic anhydride in the presence of
[
29]
p-TSA has already been reported from our laboratory. The reactions were carried
out at room temperature for the protection of aldehydes, whereas deprotection
required microwave irradiation. In continuation with our work on protection and
deprotection of aldehydes, herein we report a solvent-free synthesis of acylals from
aldehydes and acetic anhydride using silica chloride as a catalyst. The catalyst can be
filtered and reused for two more runs.
In an initial endeavor, we tried to convert anisaldehyde (1 mmol) to the corres-
ponding acylal in the presence of various solvents and also under solvent-free con-
dition, and as shown in the Table 1 the solvent-free reaction gave the best results.
For solid aldehydes (Table 2), 2.5 mmol of acetic anhydride was used to obtain
the best results. To test the applicability of our method, we prepared a series of acy-
lals from different aldehydes, and the data shown in Table 2 clearly indicate that
electron-withdrawing and electron-donating groups do not have much effect on
the yield of the product.
After the protection, the next step comes is deprotection. In a control experi-
ment, 1,1-diacetoxy-1-(4-methoxyphenyl) methane (1 mmol) was taken, and catalytic
amounts of silica chloride were added in the presence of methanol. After 40 min, we
obtained the anisaldehyde back in good yield.
To check the chemoselectivity of this reaction, a mixture of benzaldehyde
1 mmol) and acetophenone (1 mmol) was added to acetic anhydride (4 mmol) in
the presence of silica chloride and stirred at 26–28 C for 20 h (Scheme 3). Benzal-
dehyde was converted to acylals, but acetophenone remained as such. This showed
that only aldehydes could be selectively converted to geminal diacetates in the pres-
ence of keto groups.
(
ꢀ
EXPERIMENTAL
All aldehydes were commercial products and were used without further purifi-
[
6]
cation. The catalyst silica chloride was prepared as per a reported method, and
acetic anhydride was prepared from sodium acetate and acetyl chloride. Yields refer
to yield of isolated products. Melting points and boiling points were measured on a
B u¨ chi B-540 apparatus and infrared (IR) spectra were recorded on Nicolet 400D

PROTECTION/DEPROTECTION OF ALDEHYDES
1163
Table 2. Acylation of aldehydes using acetic anhydride in the presence of silica chloride under solvent-free
conditions at room temperature
a
b
Protection
Deprotection
c
c
Entry
a
Substrates
Time
Yield (%)
98
Time (min)
Yield (%)
10 min
30
89
b
c
15 min
20 min
95
94
40
45
85
80
d
e
20 min
25 min
92
90
40
40
83
89
f
35 min
20 min
86
95
55
35
79
85
g
h
i
25 min
15 min
90
95
40
82
89
30
30
j
10 min
25 min
90
91
88
82
k
35
—
d
l
20 h
20 h
ND
—
—
m
ND
—
a
All the acylals were characterized by comparison of the melting points with authentic samples [Refs. 27,
9] and by the IR spectral analysis.
2
b
Deprotection was followed by GC-MS analysis.
Isolated yields.
c
d
ND, not detected.

1164
B. DATTA AND M. A. PASHA
Scheme 3. Chemoselective protection of aldehydes.
Fourier transform (FT)–IR Instrument. Gas chromatographic (GC)–mass spectra
were obtained using a Shimadzu GC-MS QP 5050A instrument equipped with a
3
8
0-m-long and 0.32-mm-diameter BP-5 column with the column temperature
ꢀ
0–150–250 C.
General Procedure for the Protection of Aldehydes
Silica chloride (200 mg) was added to a solution of aldehyde (10 mmol) and
acetic anhydride (15 mmol) and stirred at room temperature (for a stipulated time
as indicated in Table 2). The reactions were monitored by thin-layer chromatography
(TLC; ethyl acetate–light petrol 1:9). After completion of the reaction, ether (15 mL)
was added, and the catalyst was recovered by filtration. The filtrate was washed with
saturated NaHCO solution (10 mL) followed by water (10 mL) and then dried over
3
anhydrous Na SO . The filtrate was concentrated under vacuo to get almost pure
4
2
1
,1-diacetate. Further purification was done by silica-gel column chromatography.
General Procedure for the Conversion of Acylals into Aldehydes
A mixture of 1,1-diacetate (10 mmol), methanol (5 mL), and silica chloride was
stirred at room temperature (for the time indicated in Table 2). TLC (ethyl acetate–
light petrol 1:9) was used to monitor the reaction. After completion of the reaction,
the mixture was diluted with ether (15 mL) and the catalyst was filtered, washed with
chloroform, and reused. The filtrate was washed with brine solution (15 mL) and
dried over anhydrous Na SO . The filtrate was concentrated and the product was
2
4
purified by silica-gel column chromatography.
CONCLUSION
In conclusion, we have explored silica chloride as one of the most versatile,
cost-effective, and reusable catalysts for the synthesis of 1,1-diacetates under
solvent-free condition and then deprotection of the same to aldehydes in methanol
as solvent. The advantages of our protocol are excellent yields, shorter reaction time,
and use of ecofriendly catalyst. The present method, in our opinion, is as efficient as
[29]
our previously reported method.
REFERENCES
1. Breitenbucher, J. G.; Figliozzi, G. Solid-phase synthesis of 4-aryl-1,4-dihydropyridines via
the Hantzsch three-component condensation. Tetrahedron Lett. 2000, 41, 4311–4315.

PROTECTION/DEPROTECTION OF ALDEHYDES
1165
2
. Grover, R. K.; Kesarwani, A. P.; Srivastava, G. K.; Kundub, B.; Roya, R. Base-catalyzed
intramolecular transamidation of 2-aminoquinazoline derivatives on solid phase.
Tetrahedron 2005, 61, 5011–5018.
3. (a) Kim, K. M.; Adachi, K.; Chujo, Y. Polymer hybrids of functionalized silsesquioxanes
and organic polymers utilizing the sol-gel reaction of tetramethoxysilane. Polymer 2002,
43, 1171–1175; (b) Haas, K. H.; Amberg-Schwab, S.; Rose, K.; Schottner, G. Functiona-
lized coatings based on inorganic–organic polymers (ORMOCERAs) and their combi-
nation with vapor-deposited inorganic thin films. Surface Coatings Technol. 1999, 111,
72–79.
4
. (a) Das, B.; Suneel, K.; Venkateswarlu, K.; Ravikanth, B. Sulfonic acid functionalized sil-
ica: An efficient heterogeneous catalyst for a three-component synthesis of 1,4-dihydro-
pyridines under solvent-free conditions. Chem. Pharm. Bull. 2008, 56(3), 366–368; (b)
Firouzabadi, H.; Iranpoo, N.; Hazarkhani, H.; Karimi, B. Reactions of silica chloride
(
2
SiO Cl)=DMSO, a heterogeneous system for the facile regeneration of carbonyl com-
pounds from thioacetals and ring-expansion annelation of cyclic thioacetals. J. Org.
Chem. 2002, 67, 2572–2576.
5. Kurosh Rad-Moghadam, K.; Rouhi, S. Silica-bound benzoyl chloride mediated the
solid-phase synthesis of 4H-3,1-benzoxazin-4-ones. Beilstein J. Org. Chem., 2009, 5(13),
1–4.
6. Karade, H. N.; Sathe, M.; Kaushik, M. P. Synthesis of 4-aryl substituted 3,4-dihydropyr-
idinones using silica chloride under solvent-free conditions. Molecules 2007, 12,
1341–1351.
7
8
. Shen Lin, H.; Yu-Lin, Z.; Yuan-Jiang, P.; Shi-Hua, W. Synthesis of arbutin by two-step
reaction from glucose. J. Zhejiang Univ. Sci. 2004, 5(12), 1509–1511.
. (a) Gray, W. K.; Smail, F. R.; Hitzler, M. G.; Ross, S. K.; Poliakoff, M. The continuous
acid-catalyzed dehydration of alcohols in supercritical fluids: A new approach to the clea-
ner synthesis of acetals, ketals, and ethers with high selectivity. J. Am. Chem. Soc. 1999,
121, 10711–10718; (b) Kim, K. S.; Song, Y. H.; Lee, B. H.; Hahn, C. S. Efficient and
selective cleavage of acetals and ketals using ferric chloride adsorbed on silica gel.
J. Org. Chem. 1986, 51, 404–407.
. Heravi, M. M.; Bakhtiari, K.; Taheri, S.; Oskooie, H. A. KHSO : A catalyst for the
9
4
chemoselective preparation of 1,1-diacetates from aldehydes under solvent-free con-
ditions. Green Chem. 2005, 7, 867–869.
1
1
1
0. Mitsudera, H.; Konishi, K. Synthesis and insecticidal activity of 1,3-dithianes. J. Pesticide
Sci. 1991, 16, 387–395.
1. Kochhar, K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyksha, S. R.; Pinnick, H. W.
Conversion of aldehydes into geminal diacetates. J. Org. Chem. 1983, 48, 1765–1767.
2. Banks, R. E.; Miller, J. A.; Nunn, M. J.; Stanley, P. T.; Weakley, J. R.; Ullah, Z.
Diels–Alder route to potential trichothecene precursors. J. Chem. Soc., Perkin Trans. 1.
1981, 1096–1102.
1
3. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John
Wiley and Sons: New York, 1999; (b) Gregory, M. J. Evidence for a cyclic AA1 mech-
anism in the hydrolysis of benzylidene diacetates. J. Chem. Soc. B 1970, 1201–1207.
4. Frick, J. G.; Harper, R. J. Acetals as crosslinking reagents for cotton. J. Appl. Polym. Sci.
1
1
1984, 29, 1433–1447.
5. (a) Khabazzadeh, H.; Saidi, K.; Sheibani, H. Highly efficient conversion of aromatic acy-
lals to 3,4-dihydropyrimidinones: A new protocol for the Biginelli reaction. Arkivoc. 2008,
0
1
5, 34–41; (b) Wang, X. X.; Zhang, Y. Z. Formation of a,a -bis (substituted benzylidene)
cycloalkanones from masked aldehydes promoted by samarium(III) triiodide. Chin.
Chem. Lett. 2004, 15(5), 511–514.

1166
B. DATTA AND M. A. PASHA
16. Firouzabadi, H.; Eslami, S.; Karimi, B. Neutral lithium triflate (LiOTf) efficiently
catalyzes chemoselective preparations of cyclic and acyclic dithioacetals from carbonyl
compounds, acylals, and o,o-cyclic and open-chain acetals under solvent-free conditions.
Bull. Chem. Soc. Jpn. 2001, 74(12), 2401–2406.
1
7. Roy, S. C.; Banerjee, B. A mild and efficient method for the chemoselective synthesis of
acylals from aldehydes and their deprotections catalysed by ceric ammonium nitrate.
Synlett 2002, 10, 1677–1678.
1
8. Yadav, J. S.; Reddy, B. V. S.; Srinivas, C. Indium trichloride–catalyzed chemoselective
conversion of aldehydes to gem-diacetates. Synth. Commun. 2002, 32(8), 1175–1180.
9. Jin, T. S.; Sun, G.; Li, Y. W.; Li, T. S. An efficient and convenient procedure for the prep-
aration of 1,1-diacetates from aldehydes catalyzed by H NSO H. Green Chem. 2002, 4,
1
2
3
2
55–256.
0. Sumida, N.; Nishioka, K.; Sato, T. Conversion of aldehydes into geminal dicarboxylates
acylals) catalyzed by lithium tetrafluoroborate. Synlett 2001, 12, 1921–1922.
1. Gregory, M. J. Evidence for a cyclic AA11 mechanism in the hydrolysis of benzylidene
diacetates. J. Chem. Soc. B. 1970, 1201–1207.
2. Karimi, B.; Seradj, H.; Ebrahimian, G. R. Mild and efficient conversion of aldehydes to
2
2
2
2
(
1,1-diacetates catalyzed with N-bromosuccinimide (NBS). Synlett 2000, 5, 623–624.
3. Bhattacharya, A. K.; Mujahid, M.; Natu, A. A. An efficient method for the synthesis of
acylals from aldehydes under solvent-free conditions catalyzed by antimony trichloride.
Synth. Commun. 2008, 38, 128–134.
2
2
2
4. Deka, N.; Borah, R.; Kalita, D. J.; Sarma, J. C. Synthesis of 1,1-diacetates from aldehydes
using trimethylchlorosilane and sodium iodide as catalyst. J. Chem. Res. Synop. 1998,
94–95.
5. Kochhar, K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyaksha, S. N.; Pinnick, H. W.
Protecting groups in organic synthesis, part 8: Conversion of aldehydes into geminal dia-
cetates. J. Org. Chem. 1983, 48, 1765–1767.
6. Negr o´ n, G. E.; Laura, N.; Palaciosa, L. N.; Angelesa, D.; Lomasb L.; Gavi n˜ o, R. A. Mild
and efficient method for the chemoselective synthesis of acylals from aromatic aldehydes
and their deprotections catalyzed by sulfated zirconia. J. Braz. Chem. Soc. 2005, 16(3A),
490–494.
2
7. Desai, U. V.; Thopate, T. S.; Pore, D. M.; Wadgaonkar, P. P. An efficient, solvent-free
method for the chemoselective synthesis of acylals from aldehydes and their deprotection
catalyzed by silica sulfuric acid as a reusable solid acid catalyst. Cat. Commun. 2006, 7,
508–511.
2
2
8. Aggen, D. H.; Arnold, J. N.; Hayes, P. D.; Smoter, N. J.; Mohan, R. S. Bismuth com-
pounds in organic synthesis: Bismuth nitrate–catalyzed chemoselective synthesis of acylals
from aromatic aldehydes. Tetrahedron 2004, 60, 3675–3679.
9. Manjula, K.; Pasha, M. A. Rapid and efficient method for the synthesis of acylals from
aldehydes and their deprotection catalyzed by p-toluene sulphonic acid (p-TSA). Synth.
Commun. 2007, 37, 1563–1569.
3
3
0. Mohammadpoor-Baltork, I.; Aliyan, H. Bismuth chloride, an efficient and selective
catalyst for deprotection of 1,1-diacetates. Synth. Commun. 1999, 29, 2741–2746.
1. Aggarwal, K. V.; Fonquerna, S.; Vennall, G. P. Sc(OTf) , an efficient catalyst for forma-
3
tion and deprotection of geminal diacetates (acylals): Chemoselective protection of alde-
hydes in presence of ketones. Synlett 1998, 8, 849–850.
32. Smitha, G.; Reddy, S. A facile and efficient ZrCl -catalyzed conversion of aldehydes to
4
geminal-diacetates and dipivalates and their cleavage. Tetrahedron 2003, 59, 9571–9576.
3. Ramalingam, T.; Srinivas, R.; Reddy, B. V. S.; Yadav, J. S. A mild and efficient cleavage
3
4
of gem-diacetates to aldehydes by CBr . Synth. Commun. 2001, 31, 1091–1095.