An efficient method for the oxathioacetalization of carbonyl compounds using N-bromosaccharin as a catalyst

Article abstract of DOI:10.1016/j.cclet.2012.06.007

A mild and highly chemoselective method for the preparation of oxathiolane from aliphatic and aromatic aldehydes and ketones with 2-mercaptoethanol in the presence of catalytic amount of N-bromosaccharin at room temperature is reported.

Full text of DOI:10.1016/j.cclet.2012.06.007

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 927–929
www.elsevier.com/locate/cclet
An efficient method for the oxathioacetalization of carbonyl
compounds using N-bromosaccharin as a catalyst
*
Heshmatollah Alinezhad , Shahrouz Fallahi
Faculty of Chemistry, Mazandaran University, Babolsar, Iran
Received 5 April 2012
Available online 4 July 2012
Abstract
A mild and highly chemoselective method for the preparation of oxathiolane from aliphatic and aromatic aldehydes and ketones
with 2-mercaptoethanol in the presence of catalytic amount of N-bromosaccharin at room temperature is reported.
# 2012 Heshmatollah Alinezhad. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Protection; Carbonyl compounds; Oxathioacetalization; N-Bromosaccharin
Conversion of carbonyl groups to their corresponding oxathioacetals is very important from different aspects [1].
The main reasons for the preparation of 1,3-oxathiolanes are their considerable stability under different reaction
conditions, ease of formation and removal and equality to acyl carbanions in C–C bond forming reactions [2].
A number of methods have been reported for the generating of oxathioacetal derivatives by reacting carbonyl
compounds with 2-marcaptoethanol using equimolar amount of Lewis acid such as BF3ꢀOEt2 [3], ZnCl2 [4], LaCl3
[5] and WCl6 [6]. Other methods in the literature employ NBS [7], In (OTf)3 [8], ZrCl4 [9], and OTAB [10].
Nevertheless, some of these methods have certain drawbacks such as relatively harsh reaction conditions, long
reaction times, reflux condition, expensive reagents, inconvenient procedures, using of stoichiometric amounts of
catalyst, unwanted side reaction and poor chemoselectivity. Thus, the development of mild, efficient and
chemoselective methodology for this transformation is desirable.
N-Bromosaccharin (NBSac) is a strong oxidizing and bromonating agent. This reagent has successfully been used
for regioselective cleavage of epoxides [11], oxidative cleavage of oximes [12].
In this communication, we report a mild and highly chemoselective procedure for the conversion of aliphatic and
aromatic aldehydes and ketones into 1,3-oxathiolanes using 2-mercaptoethanol and catalytic amount of NBSac in
CH2Cl2 at room temperature (Scheme 1).
1. Experimental
Materials were purchased from Merck and Aldrich companies. NBSac was prepared according to the reported
procedure [13]. Nuclear magnetic resonance spectra were recorded on a Bruker DRX-400 AVANCE spectrometer
in CDCl3 or DMSO as solvent.
* Corresponding author.
E-mail address: heshmat@umz.ir.ac (H. Alinezhad).
1001-8417/$ – see front matter # 2012 Heshmatollah Alinezhad. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.06.007

[(Scheme_1)TD$FIG]
928
H. Alinezhad, S. Fallahi / Chinese Chemical Letters 23 (2012) 927–929
O
NBSac
, rt
SH
S
O
R2
+
HO
R1
R2
CH2Cl2
R1
1
R = Alkyl,Aryl
2
R = Alkyl, H
Scheme 1. Protection of carbonyl compounds as oxathiolanes using catalytic amount of NBSac.
Carbonyl compounds (1 mmol), 2-mercaptoethanol (1.2 mmol) and the catalyst (10 mol%) in dichloromethane
were stirred at room temperature. The progress of the reaction was monitored by TLC. After completion of the
reaction, the mixture was diluted with aqueous NaOH 10% (10 mL) and it was extracted with CH2Cl2 (3 ꢁ 30 mL).
The combined organic layers were washed with 10% aqueous NaOH (10 mL) and H2O (2 ꢁ 25 mL) and then dried
over anhydrous sodium sulfate. The extracts were then concentrated under reduced pressure to afford crude products.
Further purification was achieved by chromatography on a silica-gel column to give pure product. Spectroscopic
characterization data of some compounds are given in supplementary data.
2. Results and discussion
To optimize the reaction conditions, initially we have chosen benzaldehyde as a model compound.
Oxathioacetalization of benzaldehyde (1 mmol) with 2-mercaptoethanol (1.2 mmol) was carried out in the presence
of catalytic amount of N-bromosaccharin at room temperature. We examined the effect of different solvents
(THF, CH3CN, CH2Cl2, EtOH) using NBSac. Dichloromethane was the best solvent (Table 1, entries 1–4). We also
found that the amount of catalyst had an effective influence on the reaction course. 10 mol% of catalyst gave the best
result (Table 1, entries 5–8). Then we examined the effect of different molar ratio of 2-mercaptoethanol to
benzaldehyde in the presence of NBSac in dichloromethane at room temperature for this conversion. We found that the
optimized molar ratio was 1.2:1 (Table 1, entries 9–11).
To investigate the scope of reaction, a wide variety of carbonyl compounds were protected in the form of 1,3-
oxathiolanes using 2-mercaptoethanol as the protecting group and the results are shown in Table 2. As shown in Table
1, the reaction of 2-mercaptoethanol with various aromatic aldehydes and ketone under optimal reaction conditions
afforded oxathiolanes in high to excellent yields (Table 2, entries 1–8).
To examine the chemoselectivity of this protocol, we have used the cinnamaldehyde and 4-acetylbenzaldehyde
(Table 2, entries 9–10). These reactions were completed without damage of double bond and ketone group in
cinnamaldehyde and 4-acetylbenzaldehyde, respectively. Heterocyclic compound such as thiophene-2-
carbaldehyde was successfully oxathioacetalized with 84% yield (Table 2, entry 11). The linear chain ketone
and aldehyde, i.e. 2-heptanone and hexanal were also converted to the corresponding ketal and acetal in moderate
yields (Table 2, entries 12–13). Similarly the cyclic ketones such as cyclohexanone and cyclopentanone also
worked well (Table 2, entries 14–15).
Table 1
Optimization of the preparation of 2-phenyl-1,3-oxathiolane.
Entry
Ratio of 2-mercaptoethanol
to benzaldehyde (mmol)
Catalyst (mol%)
Solvent
Time (h)
Yieldb (%)
1
1.2: 1
1.2: 1
1.2: 1
1.2: 1
1.2: 1
1.2: 1
1.2: 1
1.2: 1
0.5: 1
1: 1
10
10
10
10
–
CH3CN
EtOH
2
70
60
40
85
–
2
2
3
THF
2
4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
1.75
1.75
1.75
1.75
1.75
1
5
6
5
40
65
85
40
70
85
7
8
8
10
10
10
10
9
10
11
1.75
1.75
1.2: 1

H. Alinezhad, S. Fallahi / Chinese Chemical Letters 23 (2012) 927–929
929
Table 2
Protection of carbonyl compounds as oxathiolanes using catalytic amount of NBSac.a
Entry
Substrate
Productb
Time (h)
Yieldc (%)
Ref.
1
Benzaldehyde
2-Phenyl-1,3-oxathiolane
1.25
0.25
0.5
0.5
0.5
0.75
0.5
1.25
1.16
0.25
1.83
1
85
97
93
90
87d
83d
80
50d
90
97
84
80
80
82
80
[15]
[14]
[14]
[19]
[14]
[14]
[20]
[17]
[16]
[9]
2
4-Nitrobenzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
4-Methylbenzaldehyde
4-Methoxybenzaldehyde
2-Naphthaldehyde
Acetophenone
2-(4-Nitrophenyl)-1,3-oxathiolane
2-(4-Chlorophenyl)-1,3-oxathiolane
2-(4-Bromophenyl)-1,3-oxathiolane
2-(4-Methylphenyl)-1,3-oxathiolane
2-(4-Metoxyphenyl)-1,3-oxathiolane
2-(Naphthalen-6-yl)-1,3-oxathiolane
2-Methyl-2-phenyl-1,3-oxathiolane
2-Styryl-1,3-oxathiolane
3
4
5
6
7
8
9
Cinnamaldehyde
10
11
12
13
14
15
4-Acetylbenzaldehyde
Thiophene-2-carbaldehyde
Hexanal
1-(4-(1,3-Oxathiolan-2-yl)phenyl)ethanone
2-(2-Thienyl)-1,3-oxathiolane
[7]
2-Pentyl-1,3-oxathiolane
[16]
[16]
[18]
[18]
2-Heptanone
2-(Heptan-2-yl)-1,3-oxathiolane
Spiro[cyclohexane-1,20-[1,3]oxathiolane]
Spiro[cyclopentane-1,20-[1,3]oxathiolane]
1.5
1
Cyclohexanone
Cyclopentanone
1
a
Reaction conditions: Benzaldehyde (1 mmol), 2-mercaptoethanol (1.2 mmol), NBSac (10 mol%), room temperature, CH2Cl2.
The products characterized with 1H and 13C NMR.
b
c
d
Yields refer to pure isolated products.
With excess amount of 2-mercaptoethanol.
3. Conclusion
A novel and efficient procedure has been developed for synthesis of 1,3-oxathiolane derivatives from carbonyl
compounds and 2-mercaptoethanol in the presence of catalytic amount of NBSac. Operational simplicity, low cost of
the catalyst, high yield and excellent chemoselectivity reactions are the key features of this methodology.
Acknowledgment
We are thankful to the Research Council of Mazandaran University for the partial support of this work.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/
j.cclet.2012.06.007.
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