Highly efficient, and fast solid state deprotection of 1,3-dithianes and 1,3-dithiolanes using mercury(II) nitrate trihydrate

Article abstract of DOI:10.3390/80900663

A variety of 1,3-dithianes and 1,3-dithiolanes are deprotected in the solid state to the corresponding parent carbonyl compounds in excellent yields using mercury(II) nitrate trihydrate in a mild, efficient and fast method.

Full text of DOI:10.3390/80900663

Molecules 2003, 8, 663–669
molecules
ISSN 1420-3049
http://www.mdpi.org/
Highly Efficient, and Fast Solid State Deprotection of 1,3-
Dithianes and 1,3-Dithiolanes using Mercury(II) Nitrate
Trihydrate
Mohammad H. Habibi*, Shahram Tangestaninejad, Morteza Montazerozohori and Iraj
Mohamadpoor-Baltork
Department of Chemistry, Isfahan University, Isfahan, Iran, Tel. (+98) 311-668-0066, Fax (+98) 311-
668-7396.
* Author to whom correspondence should be addressed; e-mail habibi@sci.ui.ac.ir
Received: 30 December 2002; in revised form: 19 July 2003 / Accepted: 23 July 2003 / Published: 15
August 2003
Abstract: A variety of 1,3-dithianes and 1,3-dithiolanes are deprotected in the solid state
to the corresponding parent carbonyl compounds in excellent yields using mercury(II)
nitrate trihydrate in a mild, efficient and fast method.
Keywords: 1,3-Dithiane; 1,3-Dithiolane; Mercury(II); Deprotection; Carbonyl
compounds; Solid-state.
Introduction
1,3-Dithiane and 1,3-dithiolane derivatives are versatile intermediates in the synthesis and
interconversion of monocarbonyl and 1,2-dicarbonyl compounds. Thioacetals are often used as
protecting groups for carbonyl compounds, particularly in multistep natural product synthesis [1-2],
due to their stability towards both acidic and basic conditions. Many procedures are available in the
literature for preparing thioacetals [3], but their deprotection to the parent carbonyl compounds is not
always an easy process. In recent years various hydrolytic [4] or oxidative methods [5-6] have been
reported for dethioacetalizations and in the last two decades or so numerous reagent combinations have

Molecules 2003, 8
664
been documented for deprotection of thioacetals, including clay supported ammonium ion [7], ferric or
cupric nitrates [8], zirconium sulfonyl phosphonate [9], oxides of nitrogen [10], air/bismuth(III) nitrate
[11], Fe(phen)3(PF6)3 [12], DDQ [13], SeO2/AcOH [14], hν/pyrylium/O2 [15], N-fluoro-2,4,6-
trimethylpyridinium triflate-water system [16], methylene green/visible hν [17], SbCl5/N2 [18],
GaCl3/H2O or GaCl3/MeOH/O2 [19], (CF3CO2)2IPh [20], m-CIC6H4CO3H/CF3CO2H [21],
NaNO3/aqueous solution (NO+, H2ONO+, ClNO) or t-butyl hypochlorite (Cl+) in anhydrous CCl4 [22],
t-butyl bromide (or iodide)/DMSO [23], DMSO/HCl/H2O [24], TMSI (Br)/DMSO [25],
LiN(I-C3H7)2/THF [26], HgO/35% aqueous HBF4 [27], benzeneseleninic anhydride [28], periodic acid
-
[29], isoamyl nitrite [30], O-mesitylenesulfonyl hydroxylamine [31], Et3O+BF4 [32], MeI in moist
acetone [33] or in 96% methanol [34], ceric ammonium nitrate (CAN) in aqueous CH3CN [35], HgO-
BF3/H2O-THF [35], N-chloro-p-toluenesulphonamide (chloroamine-T) [36], 1-chlorobenzotriazole
[37], N-halosuccinimide [38], CuCl2/CuO [39] and benzyltriphenylphosphonium peroxymonosulfate
[40].
Many of these methods, however, suffer from one or more of the following disadvantages: long
reaction times, vigorous reaction conditions, the occurrence of side reactions, unavailability of the
reagents, poor yields of the desired product and furthermore, they usually often involve solvents.
Consequently, there is a need for a simple, less expensive, fast, and efficient method for deprotection
of thioketals and thioacetals.
In recent years, there has been an increasing interest in reactions that proceed in the absence of
solvents due to their reduced pollution, low costs and simplicity in process and handling. Because of
our interest in photochemical and thermal reactions of inorganic mercury compounds [41], we now
report the use of mercury(II) nitrate trihydrate as a highly efficient, fast and selective reagent for the
deprotection of thioacetals (1,3-dithiolanes and 1,3-dithianes) to the corresponding carbonyl
compounds at solid state. This is the first report for solid-state deprotection of 1,3-dithiolanes and 1,3-
dithianes with this reagent.
Results and Discussion
Deprotection of thioketals and thioacetals with mercury (II) nitrate trihydrate proceeds readily
under solid-phase conditions. Initially, we decided to explore the role of both the hydrated and
anhydrous mercury (II) nitrate in a solventless system for the deprotection of 2-(3-nitrophenyl)-l,3-
dithiane used as a model compound. In the absence of mercury (II) nitrate trihydrate no
dethioacetalization of the model compound was observed, even after prolonged reaction times. Since
deprotection of the model compound failed in the absence of mercury(II) nitrate trihydrate, the effect
of mercury(I) nitrate dihydrate, Hg2(NO3)2·2H2O was also investigated. Surprisingly, Hg2(NO3)2·2H2O
was effective, but required longer reaction times (30min.) and gave a lower yield (70%) in the solid
state. We assume that the reason that Hg2(NO3)2·2H2O did not work as well as Hg(NO3)2·3H2O is
because mercury(I) has less affinity towards the sulfur atoms of 1,3-dithio compounds than
mercury(II). Deprotection of thioacetals with mercury(II) nitrate trihydrate was also investigated in

Molecules 2003, 8
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solution phase and the results showed that the reaction was complete in 20 min. Mercury(II) chloride
did not initiated the reaction in solid phase nor in the solution. Deprotection of thioacetals did not
proceed with mercury (II) acetate in the solid phase but it was complete after ca. 45 min. in an aqueous
acetonitrile. An optimum 1:2 molar ratio of thioacetal to mercury (II) nitrate trihydrate was established
for complete deprotection of thioacetals to carbonyl compounds in solid phase.
In this method, deprotection of a thioacetal or thioketal is achieved by grinding together a mixture
of the substrate with mercury (II) nitrate trihydrate in the solid state (Scheme 1). The reaction time is
usually between 1-4 minutes. The carbonyl compounds were isolated by washing the reaction mixtures
with solvent followed by filtration. Evaporation of the filtrate under vacuum followed by flash
chromatography often produces pure carbonyl compounds in high yields (Table 1).
Scheme 1
O
Hg(NO3)2·3H2O
S
S
R
R
R
R
1
1
2
1
1
RT, solid-state
2
This method therefore offers a simple, mild, and efficient solid-state route for converting thioketals
and thioacetals to the corresponding carbonyl compounds. As evident from the results presented in
Table 1, the presence of functional groups such as NO2 and MeO affects the reaction times. This could
be the consequence of complexation between these functional groups and the mercury(II) nitrate.
Notably, aldehydes did not undergo further oxidation to their carboxylic acids under the reaction
conditions. To demonstrate the utility of the procedure, a ten-fold scale reaction was carried out under
solid-state conditions for the deprotection of 2-(3-nitrophenyl)-1,3-dithiane to afford 3-nitro-
benzaldehyde in 95% yield. It should also be noted that no exotherm or other safety problems were
observed during mixing of the starting materials and the reactions themselves.
We have proposed the possibility of formation of a complex between the dithioacetals and the
mercury in the reaction mixture. Reaction conditions suggest a non-solvolytic reaction in which
oxygen of mercury(II) nitrate acts as a nucleophilic species. A similar conclusion and mechanism has
also been proposed by Ley for deprotection of S,S-thioacetals using seleninic anhydride [28]. These
observations prompted us to also study dethioacetalization of 1,3-dithiolanes and 1,3-dithianes by
Hg(NO3)2·3H2O and Hg2(NO3)2·2H2O. The color of Hg(NO3)2·3H2O changed from white to dark
brown and then to white. Our studies showed that the rate of the reactions in the solid phase follows
the sequence: Hg(NO3)2·3H2O > Hg2(NO3)2·2H2O.

Molecules 2003, 8
Table 1. Deprotection of 1,3-dithiolanes, and 1,3-dithianes with
666
Hg(NO3)2·3H2O in a solventless system with (1:2 molar ratios,
100% conversion).
Entry
R1
R2
H
Me
H
Ph
Me
CH2Br
H
Time/min
Yields/%a
1
2
3
4
5
6
7
8
9
2-MeOC6H4
4-BrC6H4
4-ClC6H4
Ph
4-PhC6H4
4-BrC6H4
3-NO2C6H4
2-NO2C6H4
4-ClC6H4
C6H13
3
2
2
3
4
4
2
2
3
1
90
92
90
90
88
91
95
95
92
96
H
Ph
H
10
a
Yields refer to isolated products; entries 1, 3, 7, 8 and 10= dithianes, entries 2,
4, 5, 6 and 9 = dithiolanes
In order to show the usefulness of the procedure, we have compared the results of deprotection of
thioacetals by our method with some of those previously reported in the literature (Table 2). As shown
in Table 2, the yields of the products in two of the three cases examined are better with the present
method, whereas in all three cases the reaction times are substantially shorter compared to the reported
methods. Overall the results showed that mercury (II) nitrate trihydrate in the solid state is seen to be
superior to the reported reagents in terms of higher yields, shorter reaction times, mild conditions and
very easy work up.
Table2. Comparison of deprotection of 1,3–dithanes by our method with
some of those reported in the literature.
Yield (%)/Time (min)
R1
R2
Ia
IIb
IIIc (our method)
4-Cl-C6H4
3-O2N-C6H4
4-Br-C6H4
H
H
93/16
88/20
86/15
92/120
88/60
80/45
90/2
95/2
91/4
CH2Br
a Ref. [40], b Ref. [6], C our method

Molecules 2003, 8
667
Conclusions
In this study, we have introduced a new application of Hg(NO3)2·3H2O as an effective reagent for
solid-state deprotection of 1,3-dithiolanes and 1,3-dithianes. Although it offers no “green chemistry”
advantages, it is important to note that most of the reported methods for the deprotection of
1,3-dithianes and 1,3-dithiolanes use toxic reagents but this method has the advantages of very short
reaction time (1-4 min.), no side reactions, excellent yields, mild reaction conditions, a solid state
reaction and simple extraction of the products. In the other hand, those methods which might be
classified as “green chemistry” typically suffer from other disadvantages such as long reaction times,
and low yields of the products. Consequently this methodology represents a good addition to list of
methods already available for this purpose.
Experimental
General
All of the products were characterized by a comparison of their spectral (IR, 'H-NMR and TLC)
and physical data (melting and boiling points) with those of known samples [42]. All yields refer to
isolated products. NMR spectra were recorded on a Bruker AW 80 MHz in CDCl3 relative to TMS as
an internal standard. IR spectra were run on a Shimadzu IR-435 spectrophotometer. Mass spectra were
recorded on an AMD 604 spectrometer, EI-mode at 70 ev, FT-mode at 0.005 V. The purity of the
substances and the progress of the reactions were checked by TLC on silica gel or with a Shimadzu
GC-16A Gas Chromatograph instrument equipped with a flame ionization detector. All of the
reactions were carried out in the absence of solvent at room temperature in a fume hood with strong
ventilation. The carbonyl derivatives were prepared from the corresponding carbonyl compounds and
1,3-propanedithiol according to the reported procedures [3,7b].
Typical procedure for solid phase deprotection of thioacetals with mercury(II) nitrate trihydrate:
reaction of 2-(3-nitrophenyl)-1,3-dithiane.
Mercury(II) nitrate trihydrate (0.757g, 2 mmol) was added to 2-(3-nitrophenyl)-1,3-dithiane
(0.235g, 1 mmol) placed in a mortar. The reaction mixture was ground by pestle at room temperature
under solvent-free condition for 1-4 minutes. After the disappearance of starting material as monitored
by TLC, the mixture was washed at once with ethanol or acetonitrile (5 mL) and filtered. The filtrate
was evaporated under reduced pressure and the resulting crude material was purified by flash
chromatography on SiO2 (eluent: CH2Cl2) to afford 3-nitrobenzaldehyde (95%); m.p = 42ºC; IR(KBr):
ν = 3050(m), 2950(m), 1685(s), 1610(m), 1570(m), 828(m), 760(m) cm-1; 1H-NMR (CDCl3, 80MHz):
δ= 7.9 (s,1H), 8.0-8.4 (m, 4H) ppm; MS: m/e=151.

Molecules 2003, 8
668
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Sample Availability: Available from the authors.
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