A mild method for the protection of aldehydes as dithioacetals and dithiolanes catalyzed by I2 generated in situ using Fe(NO 3)3.9H2O/Nai under heterogeneous conditions

Article abstract of DOI:10.1002/jccs.200900064

Structurally diverse aromatic aldehydes were thioacetalated in a clean and efficient reaction with ethane-1,2-dithiol and thiophenol based on the use of I₂ generated in situ from Fe(NO₃)₃.9H ₂O/NaI. The reaction occurs in good to high yield in dichloromethane at room temperature and the use of toxic and corrosive molecular iodine is avoided.

Full text of DOI:10.1002/jccs.200900064

Journal of the Chinese Chemical Society, 2009, 56, 431-434
431
Note
A Mild Method for the Protection of Aldehydes as Dithioacetals and
Dithiolanes Catalyzed by I2 Generated in situ Using Fe(NO3)3.9H2O/NaI
Under Heterogeneous Conditions
Amin Rostami,a Heidar Ali Alavi Nik,b Zahra Toodeh Roostab and Ardeshir Khazaeib,*
aDepartment of Chemistry, Faculty of Science, University of Kurdistan, Sanandaj, 66135, Iran
bFaculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
Structurally diverse aromatic aldehydes were thioacetalated in a clean and efficient reaction with eth-
ane-1,2-dithiol and thiophenol based on the use of I2 generated in situ from Fe(NO3)3.9H2O/NaI. The reac-
tion occurs in good to high yield in dichloromethane at room temperature and the use of toxic and corro-
sive molecular iodine is avoided.
Keywords: Aldehydes; Ethane-1,2-dithiol; Thiophenol; Fe(NO3)3.9H2O/NaI; in situ I2;
Thioacetalization; Dithiolanation.
INTRODUCTION
The protection of the carbonyl functionality as a
CuSO4/NaI.12
dithioacetal is a common practice in multistep synthesis of
natural1 and non-natural2 products due to the group’s inher-
ent stability under both acidic and basic conditions. In ad-
dition, thioacetals are also utilized as masked acyl anions or
masked methylene functions in carbon-carbon bond form-
ing reactions.3 In the literature there are numerous methods
reported for the preparation of thioacetals from carbonyl
compounds.4-10 All of these methods have some draw-
backs such as difficulties in work-up, the requirement for
an inert atmosphere, and the use of relatively expensive re-
agents.4-10 Therefore, there is still a need to develop a sim-
ple and efficient method for thioacetalization of alde-
hydes.
RESULTS AND DISCUSSION
In our ongoing research program to develop new
synthetic methodologies for protection and deprotection
of organic functional groups,13 we have developed a sim-
ple method for dithioacetalization of various aromatic al-
dehydes in the presence of I2 generated in situ from
Fe(NO3)3.9H2O/KI under mild and heterogeneous condi-
tions (Scheme I).
It should be mentioned that molecular iodine was
generated in situ by oxidation of NaI using Fe(NO3)3.
9H2O. We measured the amount of I2 generated in situ in
CH2Cl2 by the UV-Visible spectrophotometer method (NaI
is the limiting reagent). It was found that 0.142 mmol of I2
is produced for every mmol of NaI.
Although molecular iodine is a versatile reagent in or-
ganic synthesis,11 it is highly corrosive and toxic, making
its use somewhat unattractive; in order to overcome these
disadvantages with molecular iodine, Bailey et al. reported
a convenient method for in situ generation of I2 using
In the beginning, the thioacetalization of p-methyl-
benzaldehyde with ethane-1,2-dithiol in the presence of
various salts and NaI in diethyl ether at room temperature
was studied; the results have been summarized in Table 1.
Scheme I

432 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Rostami et al.
Table 1. The thioacetalization of p-methyl benzaldehyde (1
mmol) with ethane-1,2-dithiol (2 mmol) in the presence
of various salts (0.1 mmol) and NaI (0.2 mmol) in
dichloromethane at room temperature
Table 2. The thioacetalization of p-methyl benzaldehyde (1
mmol) with ethane-1,2-dithiol (2 mmol) in the presence
of Fe(NO3)3.9H2O (0.1 mmol) and various halide salts
(0.2 mmol) in dichloromethane at room temperature
Entry
Mineral salts
Time (h) Yield (Conversion)%
Entry
Halide salts
Time (h)
Yield (Conversion)%
1
Fe(NO3)3.9H2O
Fe2(SO4)3.5H2O
FeCl3.6H2O
3
3
3
3
3
3
3
3
3
3
80
15
50
-
1
2
3
4
5
6
KI
2
2
2
2
2
2
30
70
-
2
NaI
3
KCl
NaCl
KBr
NaBr
4
ZnNO3.6H2O
CrCl3.6H2O
10
15
50
5
40
6
CuCO3.Cu(OH)2
Cu(NO3)2.3H2O
CuCl2.2H2O
7
25
10
35
-
8
9
CuSO4.5H2O
dithiol in the Fe(NO3)3.9H2O in the presence of various
halides in diethyl ether at room temperature was investi-
gated; the results have been summarized in Table 2. The re-
sult in Table 2 shows that the system of Fe(NO3)3.9H2O/
NaI gave the best result for the thioacetalization of p-meth-
yl benzaldehyde with ethane-1,2-dithiol.
10
Cu(CH3CO3)2.H2O
Among the presented salts, Fe(NO3)3.9H2O is the best one
(Table 1, Entry 1).
Therefore, we chose it for accomplishing the desired
thioacetalization of carbonyl compounds. Then the thio-
acetalization of p-methylbenzaldehyde with ethane-1,2-
As shown in Table 3, the protection of various aro-
matic aldehydes occurred as the corresponding dithioacet-
Table 3. Protection of various aldehydes as the corresponding dithioacetals catalyzed with I2 generated in situ
from Fe(NO3)3.9H2O/NaI in CH2Cl2 at room temperature
Time
(h)
Yield
(%)
Entry
Substrate
Thiol used (mmol)
HSCH2CH2SH (2 mmol)
PhSH (4 mmol)
Producta
S
CHO
1
2
5
80
95
S
SPh
17
CHO
SPh
S
3
4
5
6
7
8
HSCH2CH2SH (2 mmol)
PhSH (4 mmol)
7
85
80
90
82
87
60
CHO
H C
3
H C
3
S
SPh
CHO
16
2.5
12
8.5
5
H3C
H C
3
SPh
S
CHO
CHO
CHO
HSCH2CH2SH (2 mmol)
PhSH (4 mmol)
MeO
MeO
Br
MeO
S
SH
MeO
SH
S
HSCH2CH2SH (2 mmol)
PhSH (4 mmol)
Br
Br
S
SPh
CHO
Br
SPh
S
(H3C)2N
CHO
9
HSCH2CH2SH (2 mmol)
19
80
(H C) N
3
2
S

Protection of Aldehydes as Dithioacetals and Dithiolanes
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 433
SPh
(H3C)2N
CHO
10
11
PhSH (4 mmol)
22
8
86
75
(H C) N
3
2
SPh
S
S
CHO
HSCH2CH2SH (2 mmol)
H3C
H3C
SPh
SPh
CHO
12
13
14
PhSH (4 mmol)
HSCH2CH2SH (2 mmol)
PhSH (4 mmol)
12
16
11
90
1000
50
H C
3
H3C
S
S
CHO
Cl
Cl
Cl
Cl
SPh
SPh
CHO
S
15
16
HSCH2CH2SH (2 mmol)
PhSH (4 mmol)
2.5
11
94
90
CHO
CHO
O
O
O
O
S
SPh
SPh
a All products were characterized by comparison of their spectral data (1H-NMR; IR) with those of authentic
samples
als catalyzed with I2 generated in situ from Fe(NO3)3.
9H2O/NaI in good yields.
ditional 5 min, and the resultant mixture was filtered. The
organic layer was washed with water (25 mL), brine (25
mL) and dried over anhydrous Na2SO4. The solvent was re-
moved under reduced pressure and the reaction mixture
was passed through a short column of silica gel using
n-hexane as an eluent. Then n-hexane was evaporated to
dryness to afford the pure product.
In summary, a mild method for the in situ generation
of I2 from inexpensive starting materials, Fe(NO3)3.9H2O/
NaI, has been developed. The I2 generated in situ has been
shown to be an effective promoter for thioacetalization and
dithiolanations of aldehydes using ethane-1,2-dithiol and
thiophenol under mild, heterogeneous and neutral condi-
tions.
ACKNOWLEDGEMENT
The authors acknowledge to Bu-Ali Sina Univer-
sity Research Councils, University of Kurdistan Research
Councils, the Center of Excellence in Development of
Chemistry Methods (CEBCM) and National Foundation of
Elites (NFE) for support of this work.
EXPERIMENTAL SECTION
General procedure for thioacetalization and dithio-
lanation of aldehydes using ethane-1,2-dithiol and
thiophenol catalyzed with I2 generated in situ from
Fe(NO3)3.9H2O/NaI in CH2Cl2
Received August 18, 2008.
The aldehyde (1 mmol) and ethane-1,2-dithiol (2
mmol) or thiophenol (4 mmol) were added to a mixture of
Fe(NO3)3.9H2O (0.1 mmol) and NaI (0.2 mmol) in CH2Cl2
(5 mL). The mixture was stirred at room temperature for
the specified time (Table 3). After completion of the reac-
tion (TLC), the mixture was filtered and the solids were
washed with CH2Cl2 (5 mL). Powdered Na2S2O3 (»2 g.
portionwise) was added, the mixture was stirred for an ad-
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