1182
LETTER
An Efficient Procedure for the Preparation of Cyclic Ketals and Thioketals
Catalyzed by Zirconium Sulfophenyl Phosphonate
Massimo Curini,* Francesco Epifano, Maria Carla Marcotullio, Ornelio Rosati
Dipartimento di Chimica e Tecnologia del Farmaco Sezione di Chimica Organica, Facoltà di Farmacia, Università di Perugia,
Via del Liceo, I-06123 Perugia, Italy
Fax +39-075-5855116; E-mail: curmax@unipg.it
Received 26 April 2001
13
for the preparation of cyclic ketals. The process has
Abstract: A convenient method for the preparation of cyclic ketals
been optimized using various diols. The reaction was car-
and thioketals using zirconium sulfophenyl phosphonate as catalyst
ried out in refluxing dichloromethane using a carbonyl
is described.
compound (1.0 mmol) and the appropriate diol (2.0
Key words: acetals, catalysis, diols, thioketals, zirconium sul-
mmol) in the presence of zirconium sulfophenyl phospho-
fophenyl phosphonate
nate (25 mg) for 1-24 h (Scheme).14
It is well established that many acidic and basic solids act
as catalysts or promoters in liquid phase organic synthe-
sis.1 There are many examples of better yields, shorter re-
action times and even higher selectivities achieved as the
result of reactions carried out with heterogeneous cata-
lysts under conditions milder than those employed in con-
ventional homogeneous synthetic methods.
It was recently found that layered zirconium sulfophenyl
phosphonate2 [Zr(O3PCH3)1.2(O3PC6H4SO3H)0.8], bearing
strongly acidic -C6H4SO3H groups anchored to the inor-
Scheme
ganic layers, is an excellent catalyst for the protection/
deprotection of alcohols, phenols,3 aldehydes and ke-
tones.4 The catalyst is obtained by leaving zirconium (IV)
As shown in the Table several aldehydes and ketones gave
fluorocomplexes to decompose in a solution containing
the corresponding acetals in high yields and short reaction
m-sulfophenylphosphonic acid in a proper ratio.4 The zir-
times. It is worth noting that , -unsaturated and aromatic
conium phosphonate is formed as a microcrystalline pow-
ketones did not react with propan-1,3-diol but when bu-
der. The acid strength (Ho) of the catalyst should lie
tan-1,4-diol was employed as reactant, the corresponding
between pKa values of 5.6 and 8.2 and it is similar to
1,3-dioxepanes15 were obtained (see Table) except in the
that of hydrogen montmorillonite but higher than that of
case of 5-nonanone, 3-methylcyclohexanone and ace-
Amberlyst 15. The strongly acidic catalyst compares
tophenone.
favourably with the most common styrene-divinylben-
There have been continuing developments in the prepara-
tion of cyclic thioketals, which are important protected in-
termediates in organic synthesis.5 1,3-Dithianes and 1,3-
dithiolanes are usually obtained by protic or Lewis acid
catalyzed condensation of carbonyl compounds and dithi-
ols.5 Recently Nafion-H,16 KSF montmorillonite,17 lan-
thanum chloride18 and H-Rho zeolite19 have also been
used as heterogeneous catalysts for this purpose. The re-
action was carried out in refluxing dichloromethane using
carbonyl compounds (1.0 mmol) and the appropriate
dithiol (2.0 mmol) in the presence of the catalyst (25 mg)
(see Scheme and Table) for 0.25-2 h.14
zene sulfonic resin, does not show marked swelling phe-
nomena in the presence of apolar or slightly polar solvents
and possesses a good thermal resistance.
In continuation of our ongoing efforts to develop new
methods for the protection of functional groups, we decid-
ed to investigate the use of zirconium sulfophenyl phos-
phonate (ZrPSO3H) in the preparation of cyclic ketals and
thioketals from aldehydes and ketones.
1,3-Dioxolanes and 1,3-dioxanes are important protecting
groups for carbonyl compounds and are generally pre-
pared by the reaction of aldehydes and ketones with
ethan-1,2-diol or propan-1,3-diol in the presence of acid
catalysts under homogeneous conditions.5 Moreover,
many publications describe the use of inorganic solids
such as natural kaoline,6 acid-activated montmorillonite
K-10,7 quaternary ammonium, Al+3 or Ce+3 exchanged
montmorillonites,8-10 Al-Fe pillared montmorillonite,11
montmorillonite K-1012 and tridirectional zeolites Y and
As shown in the Table all aldehydes and ketones gave the
corresponding 1,3-dithiane and 1,3-dithiolanes in high
yields and very short reaction times, with no differences
in reactivity depending on the structure of carbonyl com-
pound or dithiol.
Synlett 2001, No. 7, 1182–1184 ISSN 0936-5214 © Thieme Stuttgart · New York