A novel approach towards dethioacetalization reactions with H 2O2-SOCl2 system

Article abstract of DOI:10.1016/j.cclet.2011.09.011

A simple and efficient protocol for the deprotection of dithioacetal, 1,3-dithianes and 1,3-dithiolanes has been developed using H₂O ₂-SOCl₂ reagent system. In addition to the absence of overoxidation products for oxidation-prone substrates, high chemoselectivity, the low cost and availability of the reagents, simplicity of the method, short reaction times, and excellent yields can also be considered as strong points for this method.

Full text of DOI:10.1016/j.cclet.2011.09.011

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 81–85
www.elsevier.com/locate/cclet
A novel approach towards dethioacetalization reactions
with H2O2–SOCl2 system
a,b,
Kiumars Bahrami a,b, , Mohammad Mehdi Khodaei
*
*
,
Maryam Tajik a, Vida Shakibaian a
a Department of Organic Chemistry, Faculty of Chemistry, Razi University, Kermanshah 67149-67346, Iran
b Nanoscience and Nanotechnology Research Center (NNRC), Razi University, Kermanshah 67149-67346, Iran
Received 17 June 2011
Available online 9 November 2011
Abstract
A simple and efficient protocol for the deprotection of dithioacetal, 1,3-dithianes and 1,3-dithiolanes has been developed using
H2O2–SOCl2 reagent system. In addition to the absence of overoxidation products for oxidation-prone substrates, high chemos-
electivity, the low cost and availability of the reagents, simplicity of the method, short reaction times, and excellent yields can also
be considered as strong points for this method.
# 2011 Kiumars Bahrami. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Deprotection; Carbonyl protecting group; Dethioacetalization; Dithioacetals; Hydrogen peroxide
Protection of carbonyls and their deprotection at some appropriate stage are important transformations often
encountered in synthesis of multifunctional natural and unnatural organic compounds because of their ubiquity and
remarkable synthetic flexibility. As a carbonyl protecting group, the S,S-acetal function has found wide use in organic
synthesis due to its easy access [1] and high stability towards both acidic and basic conditions. In addition, S,S-acetals
are often used as acyl anion equivalents in C–C bond forming reactions [2]. A variety of methods for deprotection of
dithioacetals to carbonyl compounds have been developed to date [3–11].
Nevertheless, these methods have some disadvantages such as long reaction times, toxic reagents, expensive
catalysts or not readily available reactives, and unwanted side reactions. Hence, improved methods for
dethioacetalization using cheap and less toxic reagents coupled with simple reaction conditions are required. In
this respect, we are interested in introducing an efficient reagent system to overcome these limitations.
As part of our continuing studies on the use of hydrogen peroxide in organic synthesis [12], we now wish to report a
reasonably simple and efficient method for the chemoselective dethioacetalization of dithioacetals using H2O2 in the
presence of SOCl2 in excellent yields (Scheme 1).
We have selected 2-phenyl-1,3-dithiolane (Table 1, entry 1) as a model compound to examine the effects of
different amount of H2O2 and SOCl2 in acetonitrile at room temperature. The best result (94% yield) was obtained by
carrying out the reaction with 1:2:1 mol ratios of thioacetal, H2O2 and SOCl2 for 1 min. In the absence of SOCl2 no
* Corresponding authors at: Department of Organic Chemistry, Faculty of Chemistry, Razi University, Kermanshah 67149-67346, Iran.
E-mail address: kbahrami2@hotmail.com (K. Bahrami).
1001-8417/$ – see front matter # 2011 Kiumars Bahrami. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.09.011

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K. Bahrami et al. / Chinese Chemical Letters 23 (2012) 81–85
Scheme 1. Deprotection of thioacetals.
dethioacetalization of the model compound was observed, even after prolonged reaction times. In a blank reaction,
SOCl2 alone without H2O2 was found to give low yield of product. These results mean that both a H2O2 and SOCl2 are
essential for the dedithioacetalization to occur. We also studied the use of HCl instead of SOCl2 for this purpose. Our
observations show that this reaction remained incomplete and only 53% of the desired product was obtained after 1 h.
Acetonitrile is the solvent of choice as the best results were obtained. Other solvents such as chloroform,
dichloromethane, toluene, and ethyl acetate are not as effective as acetonitrile.
To determine functional group compatibility and to investigate chemoselectivity in this reaction, a variety of
dithioacetals, 1,3-dithianes and 1,3-dithiolanes of aromatic and aliphatic aldehydes and ketones were subject to the
optimized deprotection conditions. As illustrated in Table 1, thioacetals carrying either electron-donating or electron
withdrawing substituents reacted very well to give the corresponding aldehydes in excellent yields with high purity. These
substrates selectively underwent deprotection reaction without undergoing further structural changes in their functional
groups. Forexample,acidsensitivethioacetalsuchas2-(1,3-dithiolan-2-yl)furanworked wellwithouttheformationofany
side products, which are normally observed either in the presence of protic or Lewis acids (Table 1, entry 13).
Table 1
Deprotection of dithioacetals, 1,3-dithiolanes and 1,3-dithianes with H2O2–SOCl2 in CH3CN.a
Entry
1
Substrate
Yield %b (t/min)
94 (1)
Entry
11
Substrate
Yield %b (t/min)
92 (1)
2
92 (5)
12
90 (3)
3
4
92 (1)
95 (1)
13
14
93 (1)
92 (2)
5
6
7
8
92 (1.5)
91 (5)
91 (3)
93 (1)
15
16
17
18
94 (1)
92 (3)
93 (2)
90 (6)
9
92 (1)
92 (2)
19
20
95 (1)
92 (2)
10
a
All of the products are known compounds, which were identified from their physical constants [15], their spectral data (IR, 1H NMR) and
comparison with authentic samples (superimposable IR and co-TLC).
b
Yields refer to pure isolated products.

K. Bahrami et al. / Chinese Chemical Letters 23 (2012) 81–85
83
Scheme 2. Proposed mechanism for the deprotection of thioacetals.
Acid-labile cinnamaldehyde (Table 1, entry 8), was smoothly released from respective dithiane without
overoxidation or hydrochlorination of the double bond. Most importantly, thioacetals and thioketals undergo this
reaction with equal efficiency. For example, benzaldehyde (Table 1, entry 1) is produced in 94% yield, acetophenone
(Table 1, entry 14) in 92% yield and 1,7,7-trimethylbicyclo[2.2.1]heptan-2-one, a sterically hindered ketone, (Table 1,
entry 18) in 90% yield.
We earlier reported the combination of H2O2–SOCl2 for the conversion of thiocarbonyls to carbonyl compounds
[13] as well as in the synthesis of sulfonyl chlorides and sulfonamides [14]. From these experiences, we used SOCl2 as
a convenient alternative to the gaseous HCl in the deprotection of thioacetals. The exact mechanism of the reaction is
not clear; it is acceptable to assume that the nucleophilic attack of H2O2 on SOCl2 makes oxygen atom more
Table 2
Comparison of dethioacetalization reactions by the H2O2/SOCl2 reagent system with some of those reported in the literature.
Entry
1
Substrate
Conditions in this work
Conditions in references
Time
Yield (%)
94
Time
3 h
Yield (%)
98
1 min
Cu(NO3)22.5ÁH2O/K10/solvent-free [11]
2
3
1 min
1 min
93
94
H2O2/I2/H2O2/SDS/r.t. [16]
H2O2/I2/H2O2/SDS/r.t. [16]
1 h
ꢀ100
ꢀ100
45 min
4
5
1 min
1 min
95
93
TABCOa/DMSO/CHCl3/r.t. [17]
8 min
94
Natural kaolinitic clay/solvent-free/mw [18]
Oxone-KBr/CH3CN/r.t. [19]
2 min
89
78
15 min
Natural kaolinitic clay/solvent-free/mw [18]
SiO2Cl/DMSO/CH2Cl2/r.t. [5a]
2.3 min
60 min
92
90
6
3 min
90
a
2,4,4,6-Tetrabromo-2,5-cyclohexadien-1-one.

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K. Bahrami et al. / Chinese Chemical Letters 23 (2012) 81–85
electrophilic. Therefore, the mechanism proceeds probably through intermediates 4 and 6. Then these intermediates
are hydrolyzed to the corresponding carbonyl compounds as shown in Scheme 2.
A comparison of the efficiency of this method with selected previously methods is collected in Table 2. As can be
seen, the present protocol is indeed superior to several of the other protocols.
In summary, this work demonstrates a new method for the deprotection of thioacetals to their carbonyl compounds
using H2O2–SOCl2 reagent system. In addition to the absence of overoxidation products for oxidation-prone
substrates, high chemoselectivity, the low cost and availability of the reagents, simplicity of the method, short reaction
times, and excellent yields can also be considered as strong points for this method.
1. Experimental
1.1. General
Thionyl chloride (SOCl2) and hydrogen peroxide (30%) are commercial products (Merck Chemical Company) and
were used without further purification. Thioacetals and thioketals were prepared according to reported procedures
[20]. Melting points were determined in a capillary tube and are not corrected. 1H NMR spectra were recorded on a
Bruker 200 spectrometer using TMS as internal standard. IR spectra were recorded on a Shimadzu IR-470
spectrophotometer using KBr pellets.
1.2. General procedure for dethioacetalization with H2O2–SOCl2 reagent system
A mixture of thioacetal (2 mmol), H2O2 (30%, 4 mmol, 0.4 mL) and SOCl2 (2 mmol, 0.14 mL) was stirred in
CH3CN at 25 8C for an appropriate time (Table 2). When TLC examination showed the starting material complete
disappeared. The reaction was quenched by the addition of H2O (10 mL) and the resulting mixture was extracted with
EtOAc (4Â 3 mL). The combined organic phase was dried over anhydrous sodium sulfate, and evaporated.
Chromatography on silica gel gave a pure product. An identical procedure was employed using thioketal (2 mmol),
30% H2O2 (4 mmol, 0.4 mL) and SOCl2 (2 mmol, 0.14 mL), for the deprotection of thioketals to ketones (Table 2).
Acknowledgment
We are thankful to the Razi University Research Council for partial support of this work.
References
[1] N. Komatsu, M. Uda, H. Suzuki, Synlett (1995) 984.
[2] P.C.B. Page, M.B. van Niel, J.C. Prodger, Tetrahedron 45 (1989) 7643.
[3] T.W. Greene, P.G. Wuts, Protecting Groups in Organic Synthesis, 2nd ed., John Wiley and Sons, New York, 2000.
[4] A.K. Banerjee, M.S. Laya, Russ. Chem. Rev. 69 (2000) 947.
[5] (a) H. Firouzabadi, N. Iranpoor, H. Hazarkhani, B. Karimi, J. Org. Chem. 67 (2002) 2572;
(b) F.F. Fleming, L. Funk, R. Altundas, Y. Tu, J. Org. Chem. 66 (2001) 6502.
[6] (a) J. Liu, C.-H. Wong, Tetrahedron Lett. 43 (2002) 4037;
(b) N.B. Barhate, P.D. Shinde, V.A. Mahajan, et al. Tetrahedron Lett. 43 (2002) 6031.
[7] (a) H.M. Meshram, G.S. Reddy, J.S. Yadav, Tetrahedron Lett. 38 (1997) 8891;
(b) A.T. Khan, E. Mondal, P.R. Sahu, Synlett (2003) 377;
(c) Y. Wu, X. Shen, J.H. Huang, et al. Tetrahedron Lett. 43 (2002) 6443.
[8] (a) J.G. Lee, J.P. Hwang, Chem. Lett. 24 (1995) 507;
(b) D. Crich, J. Picione, Synlett (2003) 1257;
(c) N.S. Krishanaveni, K. Surendra, Y.V.D. Nageswar, et al. Synthesis (2003) 295.
[9] (a) M. Hirano, K. Ukawa, S. Yakabe, et al. Synthesis (1997) 858;
(b) A. Kamal, E. Laxman, P.S.M.M. Reddy, Synlett (2000) 1476;
(c) M. Schmittel, M. Levis, Synlett (1996) 315.
[10] (a) B. Das, R. Ramu, M.R. Reddy, G. Mahender, Synthesis (2005) 250;
(b) N.F. Langille, L.A. Dakin, J.S. Panek, Org. Lett. 5 (2003) 575.
´
[11] G. Oksdath-Mansilla, A.B. Pen˜en˜ory, Tetrahedron Lett. 48 (2007) 6150.

K. Bahrami et al. / Chinese Chemical Letters 23 (2012) 81–85
[12] (a) K. Bahrami, Tetrahedron Lett. 47 (2006) 2009;
85
(b) K. Bahrami, M.M. Khodaei, I. Kavianinia, Synthesis (2007) 547;
(c) K. Bahrami, M.M. Khodaei, F. Naali, J. Org. Chem. 73 (2008) 6835;
(d) K. Bahrami, M.M. Khodaei, F. Naali, Synlett (2009) 569;
(e) K. Bahrami, M.M. Khodaei, Y. Tirandaz, Synthesis (2009) 369;
(f) K. Bahrami, M.M. Khodaei, M. Soheilizad, Tetrahedron Lett. 51 (2010) 4843.
[13] K. Bahrami, M.M. Khodaei, A. Farrokhi, Tetrahedron 65 (2009) 7658.
[14] K. Bahrami, M.M. Khodaei, M. Soheilizad, J. Org. Chem. 74 (2009) 9287.
[15] Aldrich Catalogue Handbook of Fine Chemicals, 2009–2010.
[16] N.G. Ganguly, S.K. Barik, Synthesis (2009) 1393.
[17] N. Iranpoor, H. Firouzabadi, H.R. Shaterian, Tetrahedron Lett. 44 (2003) 4769.
[18] B.P. Bandgar, S.P. Kasture, Green Chem. 2 (2000) 154.
[19] U.V. Desai, D.M. Pore, B.V. Tamhankar, et al. Tetrahedron Lett. 47 (2006) 8559.
[20] (a) J.S. Yadav, B.V.S. Reddy, S.K. Pandey, Synlett (2001) 238;
(b) B. Ku, D.Y. Oh, Synth. Commun. 19 (1989) 433.