A highly efficient and chemoselective method for acetalization of carbonyl compounds catalyzed by TiO2/SO42- solid superacid

Article abstract of DOI:10.1081/SCC-120021036

Various types of aldehydes and ketones could be converted to their corresponding diethyl acetals with triethylorthoformate in the presence of TiO₂/SO₄^2- solid superacid in good to excellent yield under mild reaction conditions.

Full text of DOI:10.1081/SCC-120021036

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A Highly Efficient and Chemoselective Method for
Acetalization of Carbonyl Compounds Catalyzed by
Solid Superacid
Yan-Ran Ma a , Tong-Shou Jin a , Sheng-Xun Shi a & Tong-Shuang Li a
a Department of Chemistry , College of Chemistry and Environmental Science , Hebei
University , Baoding, Hebei Province, P.R. China
Published online: 17 Aug 2006.
To cite this article: Yan-Ran Ma , Tong-Shou Jin , Sheng-Xun Shi & Tong-Shuang Li (2003) A Highly Efficient and
Chemoselective Method for Acetalization of Carbonyl Compounds Catalyzed by Solid Superacid, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:12, 2103-2108, DOI: 10.1081/
SCC-120021036
To link to this article: http://dx.doi.org/10.1081/SCC-120021036
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 12, pp. 2103–2108, 2003
A Highly Efficient and Chemoselective Method
for Acetalization of Carbonyl Compounds
Catalyzed by TiO2=SO24ꢀ Solid Superacid
*
Yan-Ran Ma, Tong-Shou Jin, Sheng-Xun Shi,
and Tong-Shuang Li
Department of Chemistry, College of Chemistry
and Environmental Science, Hebei University,
Baoding, Hebei Province, P.R. China
ABSTRACT
Various types of aldehydes and ketones could be converted to their
corresponding diethyl acetals with triethylorthoformate in the
presence of TiO2=SO24ꢀ solid superacid ingood to excellent yield
under mild reaction conditions.
Key Words: Diethyl acetals; Triethylorthoformate; Acetalization;
Carbonyl compound.
*Correspondence: Tong-Shou Jin, Department of Chemistry, College of
Chemistry and Environmental Science, Hebei University, No. 1 Hezuo Road,
Baoding 071002, Hebei Province, P.R. China; E-mail: orgsyn@mail.hbu.edu.cn.
2103
DOI: 10.1081/SCC-120021036
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2104Ma et al.
Acetalization of carbonyl compounds as dialkyl acetals is one of
most useful method for the protection of carbonyl functions in organic
synthesis.[1] Acetals have moderate stability and are easily converted
into parent compounds. For this reason, acetals have become important
tools for the synthesis of pure compounds.[2] Inthis regard, the litera-
ture shows that major attention has been paid to the preparation of
dimethyl acetals,[3–5] and diethyl analogues. Several types of Lewis acid
catalysts were introduced previously for this purpose, such as FeCl3,[6]
ZrCl4,[7] WCl6,[8] and protic acids such as HCl,[9] Amberlyst-15,[10] and
charcoal bisulfate[1] have beenused also. Each of the above methods
has its merit and some shortcomings. Some of these methods have not
been entirely satisfactory as they give low yield, have long reaction
times, problems of corrosivity of reagents, harshness of the reaction
coditions, tedious workup, and effluent pollution and nonrecoverable
catalysts. Consequently, it is desirable to develop alternative methods
for the synthesis of diethyl acetals of aldehydes and ketones using mild
and environmental friendly conditions.
TiO2=SO24ꢀ solid superacid has beenused as a catalyst inour studies
inrecent years. [11–15] In continuation of these studies, we now report that
TiO2=SO24ꢀ efficiently catalyses acetalization of carbonyl compounds
with (EtO)3CH/EtOH (absolute) at refluxing temperature under mild
conditions (Sch. 1).
As summarized in Table 1, when aldehydes and cyclic ketones 1 were
treated with triethylorthoformate 2 inthe presence of TiO 2=SO24ꢀ, the
corresponding diethyl acetals 3 were obtained in excellent yields in
absolute alcohol at refluxing temperature (Entries 1–11). Open chain
ketones gave moderate yields under same conditions (Entries 12–14).
We found that absolute alcohol as solvent is necessary in this reac-
tion. For example, 3-chlorobenzaldehyde (Entry 5) provide lower con-
versionrate (<60%) inrefluxing 95% alcohol for 7 h whereas over 95%
yield is obtained in refluxing absolute alcohol after 25 min. We also found
that cyclic aliphate ketones such as cyclopentanone (Entry 10) and cyclo-
hexanone (Entry 11) undergo acetalization reaction much faster and with
higher efficiency than the open chain ketones such as acetophenone
Scheme 1.

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Acetalization of Carbonyl Compounds as Dialkyl Acetals
2105
Table 1. Acetalization of carbonyl compounds using TiO2=SO24À as
catalyst.
Reactiontime
(min)
Isolated yield
(%)
Entry
R1
R2
1
2
C6H5
H
35
35
96
92
92
90
95
94
96
95
90
95
95
68
63
63
4-CH3C6H4
4-CH3OC6H4
3,4-(OCH2O)C6H3
3-ClC6H4
H
H
H
H
H
H
H
H
3
35
30
4
5
25
30
6
4-ClC6H4
7
3-O2NC6H4
4-O2NC6H4
C6H5CH¼CH
Cyclopentanone
Cyclohexanone
C6H5
25
25
8
9
50
35
10
11
12
13
14
35
CH3
CH3
CH3
180
180
180
4-ClC6H4
4-O2NC6H4
(Entry 12), 4-chloroacetophenone (Entry 13), and 4-nitroacetophenone
(Entry 14).
Selectivity of the synthetic methods is of great importance in organic
synthesis. Therefore, several competitive reactions between aldehydes
and open chain aromatic ketones and also between cyclic aliphate
ketones and open chain aromatic ketones were conducted successfully
with excellent chemoselectivity. The results of a set of competitive
experiments are shown in Table 2.
The catalysts need no regeneration and can be reused 10 times for the
acetalization of carbonyl compounds without significant loss of activity.
Inconclusion, we provide a highly efficient and chemoselective cat-
alyst for acetalization of carbonyl compounds under mild conditions. For
this method has operational simplicity, high yield, high chemoselectivity,
short reaction time, non-corrosive, non-polluting, and employing a
reusable catalyst.
EXPERIMENTAL
The catalyst TiO2=SO24ꢀ solid superacid was prepared according
to the Lit.[11,12] 1H NMR spectra were determined on a Varian
VXR-300S spectrometer using CDCl3 as solvent and tetramethylsilane

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2106
Ma et al.
Table 2. Selective acetalization of carbonyl compounds using
TiO2=SO24À as catalyst.
Reactiontime
(min)
Isolated yield
(%)
Entry
15
Substrate
C6H5CHO
þ
96
35
25
35
35
C6H5COCH3
3-ClC6H4CHO
þ
2
95
16
17
18
4-ClC6H4COCH3
Cyclohexanone
þ
2
95
C6H5COCH3
Cyclohexanone
þ
2
95
4-O2NC6H4COCH3
2
(TMS) as interal reference. IR spectra were obtained on a Perkin–Elmer
983G spectrometer. The products were characterized by comparisonof
their melting and boiling points with literature values.
General Procedure for Acetalization of Carbonyl Compounds
A mixture of aldehyde or ketone 1 (5 mmol), (EtO)3CH 2 (15 mmol),
and TiO2=SO24ꢀ (100 mg) was stirred at reflux for the length of time
indicated in Table 1. Absolute alcohol (5 mL) was added. The progress
of the reactionwas monitored by TLC or GC. After completionof the
reaction, the catalyst was filtered off and washed with Et2O. The filtrate
was washed with 40% NaHSO3 (15 mL) and brine (2 Â 15 mL)
successively and dried (MgSO4). Evaporation of the solvent under
reduced pressure gave almost pure product(s). Further purificationwas
proceeded by columnchromatograhy onsilica gel (light petroleum-ether
as eluent) to afford pure diethyl acetal 3.
Typical Procedure for Selective Acetalization of Benzaldehyde
vs. Acetophenone with Triethylorthoformate
To a magnetically stirred solution of benzaldehyde (3 mmol), aceto-
phenone (3 mmol), (EtO)3CH (10 mmol) inabsolute alcohol 10 mL of

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Acetalization of Carbonyl Compounds as Dialkyl Acetals
2107
reflux was added TiO2=SO24ꢀ (100 mg). After completionof the reaction,
the catalyst was filtered off and washed with Et2O, and the filtrate was
washed with brine (2 Â 15 mL) and dried (MgSO4). The organic layer was
concentrated under reduced pressure. The mixture was separated by
silical gel columnchromatography to afford phenylmethanediol diethyl
ether in 96% yield and the acetophenone was almost quantitatively
recovered.
ACKNOWLEDGMENTS
The work was supported by NSFC (29872011 and 29572039),
Education Ministry of China and Education Department of Hebei
Province (990104) and Science and Technology Commission of Hebei
Province.
REFERENCES
1. Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis,
2nd Ed.; John Wiley: New York, 1991; 175.
2. Johnson, W.S.; Harbert, C.A.; Stipanovic, R.D. Asymmetric
induction of an definic acetal cyclization. J. Am. Chem. Soc. 1968,
90, 5279.
3. Taylor, E.C.; Chiang, C.S. Trimethylorthoformate absorbed on the
montmorillonite clay K-20, an effective reagent for acetal formation.
Synthesis 1977, 467.
4. Thurkauf, A.; Jacobson, A.E.; Rice, K.C. An improved procedure
for the preparation of acetals from diaryl ketones. Synthesis
1988, 233.
5. Ishihara, K.; Karumi,Y.; Kubota, M.; Yamamoto, H. Scandium tri-
fluromethane-sulfonimide and scandium trifluoromethanesulfonate
as extremely active acetalizationcatalysts. Synlett 1996, 839.
6. Bornstein, J.; Bedell, S.F.; Drummond, P.E.; Kosloski, C.L. The
synthesis of a-amino-o-tolualdehyde diethylacetal and its attempted
conversion to pseudoisoindole. J. Am. Chem. Soc. 1956, 78, 83.
7. Firouzabadi, H.; Iranpoor, N.; Karimi, B. ZnCl4 catalyzed highly
chemoselective and efficient acetalization of carbonyl compounds.
Synlett 1999, 321.
8. Firouzabadi, H.; Iranpoor, N.; Karimi, B. Tungsten hexachloride
(WCl6), a highly efficient and chemoselective catalyst for acetalization
of carbonyl compounds. Synth. Commun. 1999, 29, 2255.

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2108
Ma et al.
9. Fife, T.H.; Jao, L.K. General acid catalysis of acetal hydrolysis. The
hydrolysis of 2-aryloxytetrahydropyrans. J. Org. Chem. 1965,
39, 1492.
10. Patwardhan, S.A.; Dev, S. Amberlyst-15, a superior catalyst for the
preparation of enol. Synthesis 1974, 348.
11. Jin, T.S.; Ma, Y.R.; Liang, D.; Li, T.S. J. Chem. Research (s)
2000, 96.
12. Jin, T.S.; Sun, X.; Li, T.S. J. Chem. Research (s) 2000, 128.
13. Jin, T.S.; Ma, Y.R.; Li, Y.; Sun, X.; Li, T.S. Synth. Commun. 2001,
31, 2051.
14. Sun, X.; Jin, T.S.; Li, T.S. Chinese J. Hebei University 2001, 21, 49.
15. Guo, J.J.; Jin, T.S.; Zhang, S.L.; Li, T.S. Green Chemistry 2001,
3, 193.
Received inthe USA October 1, 2002