J . Org. Chem. 2000, 65, 8399-8401
8399
Sch em e 1
A Sim p le Ch em oselective Meth od for th e
Dep r otection of Aceta ls a n d Keta ls Usin g
Bism u th Nitr a te P en ta h yd r a te
Kyle J . Eash, Michael S. Pulia, Laura C. Wieland, and
Ram S. Mohan*
Department of Chemistry, Illinois Wesleyan University,
Bloomington, Illinois 61701
The experimental procedure is very simple and in-
volves stirring the acetal as a solution in dichloromethane
with 25 mol % of bismuth nitrate at room temperature.
The reaction is fast and the product is isolated by a
simple aqueous workup. Bismuth nitrate is commercially
available and requires no special handling. It is insoluble
in common organic solvents and is used as a suspension.
The best yields were obtained with use of 25 mol %
reagent. Dichloromethane was found to be the best
solvent for the deprotection. Less satisfactory results
were obtained in tetrahydrofuran and diethyl ether. Less
than 50% reaction was complete in 2 h in these solvents.
The results of this study are summarized in Table 1.
Acetals derived from aromatic aldehydes underwent
smooth deprotection at room temperature. Thus, benzal-
dehyde dimethylacetal (entry 1), piperonal dimethylac-
etal (entry 2) and the terephthalaldehyde mono(diethyl
acetal) (entry 3) were all converted to the corresponding
aldehydes in good yields. Similar results were obtained
with the conjugated acetals derived from cinnamaldehyde
(entry 4) and trans-2-hexenal (entry 5). To our surprise,
acetals derived from nonconjugated aldehydes were more
resistant to the reagent. When the dimethyl acetal of
heptanal (entry 6) was subjected to the reaction condi-
rmohan@titan.iwu.edu
Received August 7, 2000
In tr od u ction
Acyclic acetals are frequently used to protect car-
bonyl compounds in the course of a total synthesis and
hence several reagents have been developed for their
deprotection.1 Some examples include p-TsOH/acetone,2a
Amberlyst-15/acetone/H2O,2b 50% trifluoroacetic acid in
CHCl3/H2O,2c aqueous dimethyl sulfoxide,2d and LiBF4 in
CH3CN.2e However, many of these methods involve the
use of corrosive reagents and elevated temperatures.
Hence several milder methods that use neutral conditions
have also been developed for the deprotection of acetals
and ketals.3a-c A selective method for cleavage of acetals
and ketals in the presence of other acid-labile protective
groups such as TBDMS has also been reported.3d The
identification of a mild and chemoselective bismuth based
reagent for the deprotection of acetals formed the basis
of this investigation. Bismuth compounds are attractive
candidates for use as reagents in organic synthesis for
several reasons. Most bismuth compounds are relatively
nontoxic, readily available at a low cost and are fairly
insensitive to small amounts of water.4 Bismuth has an
electron configuration of [Xe]4f145d106s26p3. Due to the
weak shielding of the 4f electrons (Lanthanide contrac-
tion), bismuth(III) compounds exhibit Lewis acidity.
Bismuth(III) nitrate has been used as a catalyst for the
deprotection of S,S-acetals using air.5
1
tions, no heptanal (<2% based on H NMR) formed and
the starting material was recovered unchanged. Even
after the reaction mixture was heated at reflux for 24 h
in the presence of 25 mol % Bi(NO3)3‚5H2O, over 50% of
the starting material remained. Similar results were
obtained with phenylacetaldehyde dimethyl acetal (entry
7). Interestingly, the addition of a methyl group alpha
to the acetal moiety accelerated the rate of deprotection.
Thus, with 2-phenylpropionaldehyde dimethyl acetal
(entry 8), deprotection was 50% complete after 2 h at
room temperature. Complete deprotection however re-
quired another 16 h and the addition of one more
Resu lts a n d Discu ssion
We wish to report that bismuth nitrate pentahydrate,
Bi(NO3)3‚5H2O, is an efficient reagent for the selective
deprotection of acyclic acetals derived from ketones and
conjugated aldehydes (Scheme 1).
equivalent of Bi(NO3
)3‚5H2O. The presence of a carbonyl
group alpha to the acetal moiety did not seem to acceler-
ate the reaction to any significant extent. No reaction was
observed with 2,2-diethoxyacetophenone (entry 9). In
contrast, acetals derived from aromatic as well as simple
ketones (entries 10-13) underwent smooth deprotection
at room temperature. However, reflux conditions were
required to deprotect the monacetal derived from benzil
(entry 14). Conjugation with a triple bond seemed to
accelerate the rate of the deprotection of aldehyde acetals
relative to unconjugated aldehyde acetals, but not to the
same extent as a double bond. The diethyl acetal of
phenylpropargyl aldehyde (entry 15) was only partially
converted (40%) to phenylpropargyl aldehyde even after
heating at reflux for 24 h.
* To whom correspondence should be addressed.
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley and Sons: New York, 1991.
(2) (a) Colvin, E. W.; Raphael, R. A.; Roberts, J . S. J . Chem. Soc.,
Chem. Commun. 1971, 858. (b) Coppola, G. M. Synthesis 1984, 1021.
(c) Ellison, R. A.; Lukenbach, E. R.; Chiu, C.-W. Tetrahedron Lett. 1975,
499. (d) Kametani, T.; Kondoh, H.; Honda, T.; Ishizone H.; Suzuki, Y.;
Mori, W. Chem. Lett. 1989, 901. (e) Lipshutz, B. H.; Harvey, D. F.
Synth. Commun. 1982, 12, 267.
(3) (a) Marko´, I. E.; Ates, A.; Gautier, A.; Leroy, B.; Plancher, J .-
M.; Quesnel, Y.; Vanherck, J .-C. Angew. Chem., Int. Ed. 1999, 38, 3207.
(b) J ohnstone, C.; Kerr, W.; Scott, J . Chem. Commun. 1996, 341. (c)
Balme, G.; Gore´, J . J . Org. Chem. 1983, 48, 3336. (d) Kim, K. S.; Song,
Y. H.; Lee, B. H.; Hahn, C. S. J . Org. Chem. 1986, 51, 404.
(4) (a) Reglinski, J . In Chemistry of Arsenic, Antimony and Bismuth;
Norman, N. C., Ed.; Blackie Academic and Professional: New York,
1998; pp 403-440. (b) Marshall, J . A. Chemtracts 1997, 1064-1075.
(c) Suzuki, H.; Ikegami, T.; Matano, Y. Synthesis 1997, 249-267.
(5) Komatsu, N.; Taniguchi, A.; Uda, M.; Suzuki, H. Chem. Commun.
1996, 15, 1847
As expected, cyclic acetals were much more resistant
to the reaction conditions. No reaction was observed at
room temperature with the dioxolanes (entries 16 and
17) and the starting material was recovered in quantita-
10.1021/jo001202g CCC: $19.00 © 2000 American Chemical Society
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