A convenient method for dethioacetalization of 1,3-dithiolanes and 1,3-dithianes using benzyltriphenylphosphonium peroxymonosulfate in aprotic solvent

Article abstract of DOI:10.1080/10426500214884

Benzyltriphenylphosphonium peroxymonosulfate in the presence of bismuth chloride was found to be an efficient and mild reagent for the dethioacetalization of 1,3-dithiolanes and 1,3-dithianes to the corresponding carbonyl compounds under aprotic conditions.

Full text of DOI:10.1080/10426500214884

This article was downloaded by: [University of Waterloo]
On: 31 October 2014, At: 08:56
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the Related
Elements
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gpss20
A Convenient Method for Dethioacetalization
of 1,3-Dithiolanes and 1,3-Dithianes Using
Benzyltriphenylphosphonium Peroxymonosulfate in
Aprotic Solvent
a
a
b
a
A. R. Hajipour , S. E. Mallakpour , I. Mohammadpoor-Baltork & H. Adibi
a
Isfahan University of Technology , Isfahan, Iran
b
Isfahan University , Isfahan, Iran
Published online: 27 Oct 2010.
To cite this article: A. R. Hajipour , S. E. Mallakpour , I. Mohammadpoor-Baltork & H. Adibi (2002) A Convenient Method for
Dethioacetalization of 1,3-Dithiolanes and 1,3-Dithianes Using Benzyltriphenylphosphonium Peroxymonosulfate in Aprotic
Solvent, Phosphorus, Sulfur, and Silicon and the Related Elements, 177:12, 2805-2811, DOI: 10.1080/10426500214884
To link to this article: http://dx.doi.org/10.1080/10426500214884
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur and Silicon, 2002, Vol. 177:2805–2811
Copyright �C 2002 Taylor & Francis
1
042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290146839
A CONVENIENT METHOD FOR
DETHIOACETALIZATION OF 1,3-DITHIOLANES
AND 1,3-DITHIANES USING
BENZYLTRIPHENYLPHOSPHONIUM
PEROXYMONOSULFATE IN APROTIC SOLVENT
a
a
b
A. R. Hajipour, S. E. Mallakpour, I. Mohammadpoor-Baltork,
and H. Adibia
a
Isfahan University of Technology, Isfahan, Iran and
Isfahan University, Isfahan, Iranb
(Received March 11, 2002; accepted May 10, 2002)
Benzyltriphenylphosphonium peroxymonosulfate in the presence of bis-
muth chloride was found to be an efficient and mild reagent for the
dethioacetalization of 1,3-dithiolanes and 1,3-dithianes to the corre-
sponding carbonyl compounds under aprotic conditions.
Keywords: 1,3-Dithianes; 1,3-dithiolanes; benzyltriphenylphospho-
nium peroxymonosulfate; carbonyl compounds; dethioacetalization
INTRODUCTION
The protection of certain functional groups and the deprotection of the
protected derivatives constitute important processes in the synthetic
chemistry of polyfunctional molecules including the total synthesis of
natural products. Cyclic thioacetals such as 1,3-dithiolanes and 1,3-
dithianes find wide applications in organic synthesis, particularly as
1
carbonyl protecting groups or intermediates in the reductive transfor-
2
mation of carbonyl compounds to the corresponding hydrocarbons or
3
olefins. Many procedures are available in the literature for the prepar-
4
ing of thioacetals. However, the dethioacetalization to the correspond-
ing carbonyl compounds is not an easy process because of the stability
We are thankful to the Isfahan University of Technology (IUT) Research Council for
the partial support of this work.
Address correspondence to A. R. Hajipour, Pharmaceutical Research Laboratory,
College of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran. E-mail:
haji@cc.iut.ac.ir
2
805

2
806
A. R. Hajipour et al.
of these derivatives in both acidic and basic conditions and is usually
5
6
carried out through hydrolytic or oxidative methods. Recently, for se-
lective deprotection of thioacetals in aprotic solvent manganese-based
7
oxidants (KMnO4, BaMnO4, and MnO2) also has been reported. How-
ever, some of these methods invariably require longer reaction times
and involve toxic metal ions and expensive reagents which are detri-
mental to the environment. Therefore, there is a need for a simple, less
expensive and safer method for deprotection of thioacetals.
Oxone (2KHSO5.KHSO4.K2SO4) is an inexpensive, water-soluble
and stable oxidizing reagent that is commercially available, but this
reagent is insoluble in organic solvents and buffering is needed due to
8
its acidity. Recently, we have reported benzyltriphenylphosphonium
peroxymonosulfate 1 (PhCH2Ph3PHSO5) as a mild, inexpensive, and
efficient oxidising reagent for oxidation of alcohols to aldehydes and
9
a
9b
ketones under aprotic or solvent-free conditions, oxidative depro-
tection of trimethylsilyl and tetrahydropyranyl ethers and ethylene
9
c
9d
acetals under nonaqueous conditions or microwave irradiation, con-
version of oximes, phenylhydrazones, 2,4-dinitrophenylhydrazones and
semicarbazones to carbonyl compounds in aprotic solvent, oxidation
of urazoles to triazolinediones in a solventless system9 and selective
oxidation of sulfides and thiols to the corresponding sulfoxides and
disulfides under solvent-free conditions. We now report benzyltriph-
enylphosphonium peroxymonosulfate 1 as an efficient and selective
reagent for the deprotection of 1,3-dithiolanes 2a–d and 1,3-dithianes
9e
f
9
g
2
e–w to the corresponding carbonyl compounds 3a–w under aprotic
and nonaqueous conditions.
Benzyltriphenylphosphonium peroxymonosulfate 1, a mild, effi-
cient, stable, and cheap reagent, is a white powder, quite soluble in
dichloromethane, chloroform, acetone, and acetonitrile and insoluble
in nonpolar solvents such as carbon tetrachloride, n-hexane and di-
ethyl ether. This reagent is readily prepared by the dropwise addition
of an aqueous solution of Oxone to an aqueous solution of benzyltriph-
enylphosphonium chloride in quantitative yield at room temperature
9
and could be stored for months without losing its potency. The amounts
�
of HSO in this reagent have been determined by an iodometric titra-
5
10
tion method and the measurements are consistent with almost 99%
by weight of active oxidising agent.
RESULTS AND DISCUSSION
Deprotection of thioacetals with reagent 1 proceeds under nonaqueous
conditions. Initially, the effect of various solvents such as Et2O, CH2Cl2,

Convenient Method for Dethioacetalization
2807
THF, CHCl3, and CH3CN on the deprotection of 2-(3-nitrophenyl)-1,3-
dithiane 2f as a model compound with reagent 1 in the presence of
bismuth chloride at reflux was examined. Only acetonitrile was a suit-
able solvent for this oxidation system. Then, we explored the role of the
reagent 1 in the presence of hydrated and anhydrous metal salts such
as ZnCl2, FeCl3.6H2O, AlCl3, and BiCl3 in dry aprotic solvent for the
deprotection of 2f. It was found that BiCl3 was effective metal salt for
the promotion of the reaction in dry acetonitrile. Addition of BiCl3 in
dry acetonitrile under reflux in the absence of reagent 1 did not effect
any changes on dethioacetalization of 2f after prolonged reaction times.
The reagent 1 also was an ineffective compound for deprotection of 2f
in the absence of BiCl3 in dry acetonitrile. The optimum molar ratio of
thioacetal, to BiCl3 to oxidant 1 (1:1:2) is found to be ideal for complete
deprotection of thioacetals 2a–w to carbonyl compounds 3a–w while
the reaction remains incomplete with lesser amounts for example 1:1:1
and 1:1:1.5.
By using this method, deprotection of a thioacetal is achieved by
stirring a homogeneous mixture of a thioacetal 2, BiCl3, and a twofold
excess of reagent 1 in refluxing acetonitrile. The reaction time is usually
between 1–6 h. The carbonyl compounds 3 are isolated by filtering the
reaction mixture followed by washing the solid residue with solvent.
Evaporation of filtrate under vacuum followed by flash chromatography
on SiO2 often produces pure carbonyl compound 3 in high yield (Table I
and Scheme 1).
SCHEME 1
This method offers a simple, mild, and efficient route for converting
thioacetals to the corresponding carbonyl compounds. As evident from
the results presented in Table I, functional groups such as NO2 and
MeO increase the duration of reaction. This could be the effect of pro-
ducing complexes between these functional groups with BiCl3. Notably,
aldehydes did not undergo further oxidation to their carboxylic acids
under the reaction conditions. To demonstrate the utility of the pro-
cedure described here, a macroscale reaction (10 g) was carried out at

2
808
A. R. Hajipour et al.
TABLE I Deprotection of 1,3-Dithianes and
1
,3-Dithiolanes with Reagent 1 in the Presence of
a,b
Bismuth Chloride in Refluxing Acetonitrile
Product
R1
R2
n
Time (h) Yield (%)c
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
Ph
Me
Me
H
Me
H
H
H
H
CH2Br
—
1
1
1
1
2
2
2
2
2
2
2
3
4
2
6
6
6
3
4
2
95
88
87
96
85
87
90
91
85
95
4-Cl C6H4
2-MeOC6H4
3-Pyridyl
2-O2N C6H4
3-O2N C6H4
4-O2N C6H4
4-Cl C6H4
4-Br C6H4
j
3
3
3
3
3
3
3
3
3
3
3
k
l
Ph
H
2
2
2
2
2
2
2
2
2
2
2
1
5
2
3
3
2.5
4
3
1
99
85
98
95
94
92
88
89
95
86
90
Me2CHCH2
4-Cl C6H4
Ph
2-Pyridyl
4-Cl C6H4
2-MeOC6H4
4-MeOC6H4
Ph
Me
Me
Ph
Ph
Ph
H
H
Me
H
m
n
o
p
q
r
s
t
u
CH3(CH2)5
5
4
—
3
3
v
—
H
2
2
4
1
87
91
w
aSubstrate/BiCl3/Oxidant (1:1:2).
b
11
Confirmed by comparison with known samples.
c
Yield of isolated carbonyl compound after purification.
reflux condition for the deprotection of 2-methyl-2-(4-chlorophenyl)-1,3-
dithiolane 2b to afford 4-chloroacetophenone 3b in 91% yield.
A comparison of the results of deprotection of thioacetals by our
7
method (I) with those reported for MnO2/AlCl3 (II), Oxone/wet Al2O3
6e
6h
(
III) and SeO2 (IV) is shown in Table II. This reagent is superior
to reported reagents in terms of high yield and the amount of oxidant
required.

Convenient Method for Dethioacetalization
2809
TABLE II Comparison of Deprotection of Thioacetals
by Our Method with Those Reported in the Literature
Yield (%)/Time (min)
R1
R2
n
Ia
IIb
IIIc
IVd
Ph
-Cl C6H4
Ph
H
H
Me
2
2
1
99/60
91/180
95/120
96/90
92/120
—
70/50
—
91/120
—
—
98/25
4
aSubstrate/PhCH2Ph3PHSO5/BiCl3 (1:2:1).
b
Substrate/MnO2/AlCl3 (1:7:1.5).
c
Substrate/Oxone/wet Al2O3 (1:5).
d
Substrate/SeO2 (1:5).
In conclusion, we report a new and efficient methodology for the
regeneration of aldehydes and ketones from thioacetals under apro-
tic conditions. The stability, routine preparation of the reagent and
easy work-up make this method a novel and useful one relative to the
present methodologies for regeneration of carbonyl compounds from
thioacetals.
EXPERIMENTAL
General
All of the yields refer to isolated products after purification. All of the
1
products were characterized by comparison of their spectral (IR, H-
NMR, and TLC) and physical data (melting and boiling points) with
1
1
1
those of authentic samples. All H-NMR spectra were recorded at
0 MHz in CDCl3 relative to TMS as an internal standard and IR spec-
9
tra were recorded on Shimadzu 435 IR spectrometer. The reagent 1
9
was prepared according to our previously reported procedures. The
carbonyl derivatives were prepared from the corresponding carbonyl
compounds and 1,2-ethanedithiol and 1,3-propanedithiol according to
4
the reported procedures.
Deprotection of 1,3-Dithiolanes with Reagent
1
in Refluxing Acetonitrile
General Procedure
In a round-bottom flask (25 mL) equipped with a condenser and a
magnetic stirrer, to a solution of 1,3-dithiolane 2a–d (1 mmol) and bis-
muth chloride (0.315 g, 1 mmol) in dry acetonitrile (5 mL) was added

2
810
A. R. Hajipour et al.
benzyltriphenylphosphonium peroxymonosulfate 1 (0.7 g, 2 mmol). The
reaction mixture was stirred under reflux conditions for the time spec-
ified in Table I. After disappearance of starting material monitored
by TLC, the mixture was cooled to room temperature, filtered and the
filter cake washed with acetonitrile (10 mL). The filtrate was evapo-
rated under reduced pressure. The crude product was purified by flash
chromatography on SiO2 (eluent: cyclohexane) affording the desired
carbonyl compound 3a–d.
Deprotection of 1,3-Dithianes with Reagent 1
in Refluxing Acetonitrile
General Procedure
In a round-bottom flask (25 mL) equipped with a condenser and a
magnetic stirrer, to a solution of 1,3-dithiane 2e–w (1 mmol) and bis-
muth chloride (0.315 g, 1 mmol) in dry acetonitrile (5 mL) was added
benzyltriphenylphosphonium peroxymonosulfate 1 (0.7 g, 2 mmol). The
reaction mixture was stirred under reflux conditions for the time spec-
ified in Table I. After disappearance of starting material monitored by
TLC, the mixture was cooled to room temperature and filtered off. The
filter cake was washed with acetonitrile (10 mL) and the filtrate was
evaporated under reduced pressure to afford the crude carbonyl com-
pound. The crude product was purified by flash chromatography on SiO2
(
eluent: cyclohexane) affording the carbonyl compound 3e–w.
Macroscale Deprotection of 1,3-Dithiolanes
Typical Procedure
In a round-bottom flask (1 L) equipped with a condenser and a mag-
netic stirrer, to a solution of 2-methyl-2-(4-chlorophenyl)-1,3-dithiolane
2b (10 g, 43.3 mmol) and bismuth chloride (13.6 g, 43.3 mmol) in dry
acetonitrile (200 mL) was added benzyltriphenylphosphonium peroxy-
monosulfate 1 (30.31 g, 86.6 mmol). The reaction mixture was stirred
under reflux conditions for 3 h. After disappearance of starting material
monitored by TLC, the reaction mixture was cooled to room tempera-
ture and filtered through a sintered glass funnel and the filter cake
was washed with acetonitrile (150 mL). The filtrate was evaporated
under reduced pressure and the resulting crude material was puri-
fied by flash chromatography on SiO2 (eluent: cyclohexane) to afford
�
11
4
-chloroacetophenone 3b (6.06 g, 91%), bp 231–232 C/760 Torr (Lit.
�
bp 232 C/760 Torr). IR (KBr): � = 3050 (m), 2890 (m), 1680 (s), 1590 (s),
�
1 1
1
�
400 (m), 1250 (s), 830 (m), 760 (m) cm . H-NMR (CDCl3, 90 MHz):
= 2.6 (s, 3H), 7.4–7.7 (d, 2H, J= 6 Hz), 7.9–8.2 (d, 2H, J= 6 Hz) ppm.

Convenient Method for Dethioacetalization
2811
REFERENCES
[
[
1] (a) T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis (Wiley,
New York, 1991); (b) B. C. Ranu and A. R. Das, J. Org. Chem., 56, 4796 (1991).
2] M. Numazawa, A. Mutsumi, K. Hoshi, M. Oshibe, E. Ishikawa, and H. Kigawa,
J. Med. Chem., 34, 2496 (1991).
[
[
3] L. L. Yeung, Y. C. Yip, and T.-Y. Luh, J. Org. Chem., 55, 1874 (1990).
4] (a) H. Firouzabadi, N. Iranpoor, and B. Karimi, Synthesis, 58, (1999); (b) D. Seebach
and E. J. Corey, J. Org. Chem., 40, 231 (1975); (c) B. T. Groblel and D. Seebach,
Synthesis, 357 (1977); (d) R. P. Hatch, J. Shringarpure, and S. M. Weinreb, J. Org.
Chem., 43, 4172 (1978); (e) J. A. Marshall and J. L. Belletire, Tetrahedron Lett., 871
(1971).
[
[
5] A. Lebouc, J. Simonet, J. Gelas, and A. Dehbi, Synthesis, 320 (1987).
6] (a) H. Firouzabadi, N. Iranpoor, and M. A. Zolfigol, Bull. Chem. Soc. Jpn., 71,
2
169 (1998); (b) R. S. Varma and R. K. Saini, Tetrahedron Lett., 38, 2633 (1997);
(c) H. M. Meshram, G. S. Reddy, and J. S. Yadav, Tetrahedron Lett., 38, 8891 (1997);
(d) M. Curini, M. C. Marcotullio, E. Pisani, and O. Rosati, Synlett., 769 (1997);
(e) M. Curini, P. Ceccherelli, M. C. Marcotullio, F. Epifano, and O. Rosati, Synlett.,
7
67 (1996); (f) N. Komatsu, A. Taniguchi, M. Uda, and H. Suzuki, Chem. Com-
mun., 1847 (1996); (g) M. Schmittel and M. Levis, Synlett., 315 (1996); (h) S. A.
Haroutounian, Synthesis, 39 (1995); (i) M. Hirano, K. Ukawa, S. Yakabe, J. H. Clark,
and T. Morimoto, Synthesis, 858 (1997); (j) J. G. Lee and J. P. Hwang, Chem. Lett.,
5
07 (1995); (k) H. M. Meshram, G. S. Reddy, G. Sumitra, and J. S. Yadav, Synth.
Commun., 29, 1113 (1999).
[
[
[
7] H. Firouzabadi, H. Hazarkhani, B. Karimi, U. Niroumand, and S. Ghassamipour,
Fourth International Electronic Conference on Synthetic Organic Chemistry
(ECSOC-4), September 1–30 (2000).
8] (a) A. R. Hajipour, Indian J. Chem., 36B, 1069 (1997); (b) A. R. Hajipour and
N. Mahboubkhah, Org. Prep. Proced. Int., 31, 112 (1999); (c) B. Meunier, New J.
Chem., 16, 203 (1992).
9] (a) A. R. Hajipour, S. E. Mallakpour, and H. Adibi, Phosphorus, Sulfur, and
Silicon, 167, 71 (2000); (b) A. R. Hajipour, S. E. Mallakpour, and H. Adibi, Chem.
Lett., 460 (2000); (c) A. R. Hajipour, S. E. Mallakpour, I. Mohammadpoor-Baltork,
and H. Adibi, Phosphorus, Sulfur, and Silicon, 165, 155 (2000); (d) A. R. Hajipour,
S. E. Mallakpour, I. Mohammadpoor-Baltork, and H. Adibi, Synth. Commun., 31,
1
625 (2001); (e) A. R. Hajipour, S. E. Mallakpour, I. Mohammadpoor-Baltork, and
H. Adibi, Synth. Commun., 31, 3401 (2001); (f) A. R. Hajipour, S. E. Mallakpour,
and H. Adibi, Chem. Lett., 164 (2000); (g) A. R. Hajipour, S. E. Mallakpour, and H.
Adibi, Phosphorus, Sulfur, and Silicon. (in press).
[
[
10] B. M. Trost and R. Braslau, J. Org. Chem., 53, 532 (1988).
11] Aldrich Catalogue Handbook of Fine Chemicals (1994–1995).