Highly efficient and chemoselective interchange of 1,3-oxathioacetals and dithioacetals to acetals promoted by N-halosuccinimide

Article abstract of DOI:10.1016/S0040-4020(02)00389-7

Highly efficient interconversion of a range of 1,3-oxathiolanes, 1,3-dithiolanes and 1,3-dithianes to their acetals at ambient temperature using N-bromosuccinimide or N-chlorosuccinimide and different types of alcohols and diols was investigated.

Full text of DOI:10.1016/S0040-4020(02)00389-7

TETRAHEDRON
Pergamon
Tetrahedron 58 82002) 4513±4516
Highly ef®cient and chemoselective interchange
of 1,3-oxathioacetals and dithioacetals to acetals promoted
by N-halosuccinimide
Babak Karimi,p Hassan Seradj and Jafar Maleki
Department of Chemistry, Institute for Advanced Studies in Basic Sciences ꢀIASBS), P.O. Box 45195-159, Gava Zang, Zanjan, Iran
Received 5 November 2001; accepted 5 April 2002
AbstractÐHighly ef®cient interconversion of a range of 1,3-oxathiolanes, 1,3-dithiolanes and 1,3-dithianes to their acetals at ambient
temperature using N-bromosuccinimide or N-chlorosuccinimide and different types of alcohols and diols was investigated. q 2002 Published
by Elsevier Science Ltd.
1. Introduction
examples of conversion of dithioacetals to the correspond-
ing O,O-acetals using methyl-¯uorosulfonate.4 There are, to
our knowledge, no report presenting the interconversion of
oxathioacetals to their acetals. Consequently, the develop-
ments of new and general methods for this purpose are being
pursued. In our development of new methods for functional
group transformation, we are especially interested in
exploring the potential use of N-bromosuccinimide
8NBS) as a relatively neutral and mild catalyst in organic
chemistry.6 In continuation of these studies, herein, we wish
to report a new protocol for the mild and rapid transfor-
mation of a variety of 1,3-oxathiolanes and their S,S-analogs
to the corresponding cyclic and open-chain O,O-acetals
using NBS or N-chlorosuccinimide 8NCS) 8Scheme 1).
The protection of carbonyl compounds as acetals or their
sulfur analogs is one of the most widely used and versatile
transformations in organic synthesis, as testi®ed by a large
number of reagents and methods that have been devised to
accomplish this functional group interconversion.1 Among
the carbonyl protective groups, 1,3-oxathioacetals and
1,3-dithioacetals have an especial place in organic
chemistry. 1,3-Oxathioacetals are considerably more stable
than the corresponding O,O-acetals under acidic conditions,
but compared with the S,S-acetals are more easily depro-
tected. Among this, both oxathioacetals and dithioacetals
are also of importance because they can be used as pre-
cursors for acyl anion equivalent displaying reactivity
umpolung.2,3 A major problem during many multi-step
syntheses is how to protect a carbonyl group from various
types of reagents and reaction conditions. One way to attain
this goal is the direct interchange between two chemically
different carbonyl-protecting groups without going through
the free carbonyl compound. Such a direct interchange, as
previously described by Corey and Hase4a can remove
interference by the original protecting group.4 For example,
replacement of thioacetal by acetal could permit an oxi-
dation or halogenation process not possible in the presence
of a sulfur-containing group.5
As shown in Table 1, in the presence of NBS 81 equiv.),
different types of 1,3-oxathiolanes of aldehydes were
rapidly and ef®ciently converted to the corresponding
1,3-dioxanes or 1,3-dioxolanes upon treatment with dry
1,3-propanediol 83 equiv.) or dry 1,2-ethanediol 82.5
equiv.), respectively, under mild reaction conditions
8Method A) 8Table 1, entries 1±9). The method can also
effectively conducts interchange of 1,3-oxathiolanes of
aliphatic as well as aromatic ketones under nearly similar
reaction conditions 8Table 1, entries 10±19).
R3O OR3
NBS (1-1.2 equiv.), R3OH
Method A or B, rt, 5 min
O
R1
S
R2
2. Results and discussion
R1
R2
A literature search shows that, although, there are some rare
Method A = CH2Cl2, diol (3 equiv.)
Method B = Absolute MeOH or EtOH
R3 = Me, Et, -(CH2)2- or -(CH2)3-
Keywords: protecting groups; 1,3-oxathioacetals; 1,3-dithioacetals; N-halo-
succinimide; acetals.
p
Corresponding author. Tel.: 198-241-4242239; fax: 198-241-4249023;
e-mail: karimi@iasbs.ac.ir
Scheme 1.
0040±4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020802)00389-7

4514
B. Karimi et al. / Tetrahedron 58 ꢀ2002) 4513±4516
Table 1. Interconversion of 1,3-oxathiolanes to O,O-acetals using NBS at room temperature
Entry
R1
R2
R3
Substrate/alcohol/NBS 8ratio)
Method
Yielda 8%)
1
2
3
4
5
6
7
8
Ph
Ph
H
H
H
H
H
H
H
H
±8CH2)3±
±8CH2)2±
±8CH2)3±
±8CH2)2±
±8CH2)3±
±8CH2)3±
±8CH2)2±
±8CH2)3±
±8CH2)2±
±8CH2)3±
±8CH2)2±
±8CH2)3±
±8CH2)3±
±8CH2)3±
±8CH2)2±
±8CH2)3±
±8CH2)3±
±8CH2)2±
1:3:1
1:2.5:1
1:3:1
1:2.5:1
1:3:1
1:3:1
A
A
A
97
95
89
95
94
90
93
92
85
91
95
89
86
77
89
92
88
92
4-ClC6H4
4-ClC6H4
4-8MeO)C6H4
4-8NO2)C6H4
4-8NO2)C6H4
PhCHvCH
PhCH2
A
Ab
Ab
A
1:3:1
1:3:1
9
H
1:2.5:1
1:4:1.2
1:3:1.2
1:4:1.2
1:4:1.2
1:4:1.3
1:4:1.3
1:3:1.2
1:4:1.3
1:4:1.3
A
A
A
A
10
11
12
13
14
15
16
17
18
Ph
Ph
CH3
CH3
CH3
CH3
CH3
CH3
Ph
4-ClC6H4
4-8Ph)C6H4
4-8NO2)C6H4
4-8NO2)C6H4
Ph
A
Ab
Ab
A
PhCH2CH2
PhCH2CH2
CH3
CH3
A
A
19
±8CH2)3±
1:4:1.3
A
91
20
21
22
23
24
25
Ph
Ph
H
H
H
CH3
CH3
CH3
Me
1:3 mL:1
Bb
92
98
95
98
92
89
b
Et1:3 mL:1
Et1:5 mL:1.1
Et1:5 mL:1.2
Et1:5 mL:1.3
Et1:5 mL:1.3
B
B
B
B
B
b
b
b
b
PhCHvCH
Ph
4-8NO2)C6H4
PhCH2CH2
Method A: CH2Cl2, rt. Method B: absolute ethanol or methanol was used as solvent, reaction time: 5 min unless otherwise stated.
Isolated yields.
The reactions were completed after 10 min.
a
b
Using this study, we have also discovered that the reaction
of various types of 1,3-oxathiolanes in the presence of
absolute ethanol and methanol as solvent 83±5 mL)
furnished the corresponding diethyl and dimethyl acetals,
respectively, in good to excellent yields 8Table 1, entries
20±25). It is worth mentioning that the presence of electron
withdrawing substituents on aromatic rings of 1,3-oxathio-
lanes does not affect the ef®cacy of the transformation
8Table 1, entries 6, 7, 14, 15, 24). Among different solvents
such as THF, CH3CN, CHCl3 and CH2Cl2, dichloromethane
turned out to be a suitable solvent for this transformation.
were formed. We therefore researched another protocol that
would allow such a transformation. During this study
we discovered that different types of 1,3-dithianes and
1,3-dithiolanes derived from the corresponding ketones
using 1,3-propanediol 87 equiv.) upon the slow and portion-
wise addition of NCS 81.2 equiv.) or NBS 81.2±1.4 equiv.)
were converted to their 1,3-dioxanes in good yields 8Method
C) 8Table 2, entries 9±11 and 14±18). Nevertheless, even
under this condition, interchanging of dithioacetals of
aromatic ketones bearing electron withdrawing groups,
affording the corresponding acetals in low yields 8Table 2,
entries 12 and 13).
Furthermore, although there are a variety of procedures for
conversion of acetals to the corresponding dithioacetals,7
less attention has been paid to the reverse transformation.4,5
We hypothesized that the present protocol might also
equally applied for interconversion of 1,3-dithioacetals to
their O,O-acetals. As can be seen in Table 2, 1,3-dithiane
and 1,3-dithiolanes of aldehydes were effectively and
rapidly converted to the corresponding 1,3-dioxanes using
NBS 81.0 equiv.) in the presence of 3 equivalents of
1,3-propanediol 8entries 1±7).7
The chemical transformations would be of more practical
importance if they were accompanied with high degree of
chemoselectivity. In our previous report on the new
applications of NBS, we observed that the cleavage of
1,3-oxathiolanes is much faster than 1,3-dioxolanes and
1,3-dioxanes. Moreover, we have observed that the presence
of a molar excess of organic bases such as DABCO or
pyridine in the reaction medium, does not affect con-
siderably the rate of cleavage of 1,3-oxathiolanes, but
does completely retard the deprotection of O,O-acetals
8Scheme 2). Based on these observations, it seemed
plausible that the described system could promote chemo-
selective interchange of 1,3-oxathiolanes and 1,3-dithio-
acetals in the presence of acid-sensitive substrates such
as O,O-acetals. Indeed, 2-phenyl-1,3-oxathiolane were
converted to the corresponding 1,3-dioxane in the presence
of 2-phenyl-1,3-dioxolane with almost complete chemo-
selectivity 8Scheme 2). The method even tolerates more
In the cases that absolute ethanol or methanol were used
as solvent 85 mL), the corresponding diethyl acetals or
dimethyl acetals were formed, respectively, in excellent
yields under similar reaction conditions 8Table 2, Method
A, entries 6 and 7). Interestingly, attempted interconversion
of dithioacetals of ketones under similar reaction con-
ditions of Method A failed to provide the corresponding
O,O-acetals in satisfactory yield and a mixture of products

B. Karimi et al. / Tetrahedron 58 ꢀ2002) 4513±4516
4515
Table 2. Conversion of dithioacetals to the corresponding acetals using
NBS or NCS under mild reaction conditions
ditions and the high yield of the product can be considered
as the advantages of the present protocol. Work on other
reactions promoted by NBS and related compounds are
currently underway in our laboratories.
Entry
R1
R2
Method
n
Yielda 8%)
3. Experimental
1
2
3
4
5
6
7
8
Ph
Ph
H
A
A
A
A
0
1
1
1
1
0
0
1
1
1
1
0
1
1
95
90
93
96
80
92
86
89
92
93
87
60e
30e
90
All yields refer to isolated products unless otherwise stated.
The products were puri®ed by column chromatography and
the purity determination of the products were accomplished
by GLC on a Shimadzu model GC-8A instrument or by TLC
on Silica-gel polygram SIL G/UV254 plates. IR spectra
H
H
H
H
H
H
Ph
4-8CH3)C6H4
4-8MeO)C6H4
PhCHvCH
Ph
Ph
Ph
A
Ab
Ac
A
1
were record on a Vector 22 Bruker spectrophotometer. H
CH3 Cd
NMR and 13C NMR spectra were recorded on a Bruker
Avance 250 MHz spectrometer in CDCl3 as the solvent
and TMS as internal standard. Most of the products are
known and all of the isolated products gave satisfactory
IR spectra. However, some of the selected spectra are as
follows.
9
Ph
10
11
12
13
14
4-8Cl)C6H4
4-8Ph)C6H4
4-8NO2)C6H4
4-8NO2)C6H4
PhCH2CH2
CH3
CH3
CH3
CH3
CH3
C
C
C
C
C
15
16
C
C
0
0
78
89
3.1. General procedure for interchange of 1,3-oxathio-
lanes to acetals
17
C
C
0
0
70
91
To a stirred solution of 1,3-oxathiolane 82 mmol) and diol
85±8 mmol, Procedure A in dry CH2Cl2 815 mL) was added
NBS 82±2.6 mmol), and the resulting mixture was stirred
for 5 min at room temperature. The progress of the reaction
was monitored by TLC or GC. After completion of the
reaction, the mixture was diluted with aqueous NaOH
820 mL) and it was extracted with CH2Cl2 83£30 mL2).
The combined organic layers were washed with 10%
aqueous NaOH 810 mL) and water 82£25 mL2) and dried
over anhydrous sodium sulfate. The extracts were then
concentrated under reduced pressure to afford crude
products. Further puri®cation was achieved by chroma-
tography on a silica-gel column to give pure product8s).
18
a
Yields refer to isolated products unless otherwise stated.
Reactions were performed in absolute 5 mL EtOH as solvent without
1,3-propanediol.
Reactions were performed in 5 mL absolute MeOH as solvent in the
absence of 1,3-propanediol.
Method C: diol 87 equiv.) and NBS or NCS 81.2±1.4 equiv); catalyst was
added portionwise to the reaction mixture.
A complex mixture of products was formed.
b
c
d
e
3.2. General procedure for interchange of dithioacetals
to acetals
acid-sensitive functional groups such as THP ethers
8Scheme 2).
To a stirred solution of 1,3-dithiolanes or 1,3-dithianes
82 mmol) and 1,3-propanediol 86 mmol, Procedure A or
14 mmol, Procedure B) in dry CH2Cl2 815 mL) was added
NBS 8Method A, 2.0 mmol) or NBS 8Method C,
2.4±2.8 mmol, portionwise), and the resulting mixture was
stirred for 5±10 min at room temperature. The progress of
the reaction was monitored by TLC. After completion of the
reaction, the mixture was diluted with aqueous NaOH
820 mL) and it was extracted with CH2Cl2 83£30 mL2).
The combined organic layers were washed with 10%
aqueous NaOH 810 mL) and water 82£25 mL2) and dried
over anhydrous sodium sulfate. The extracts were then
concentrated under reduced pressure to afford crude
products. Further puri®cation was achieved by chroma-
tography on a silica-gel column to give pure product8s).
In summary, we have introduced a new and ef®cient method
for the interconversion of dithioacetals and oxathioacetals
into their O,O-acetals without going through the free
carbonyl compounds. To the best of our knowledge, this
is the ®rst example of direct conversion of oxathioacetals
to the corresponding acetals without going through their
parent carbonyl compounds. Simplicity of the procedures,
easy workup of the reaction products, mild reaction con-
S
O
O
100
100
S
(3 equiv.), NBS (1 equiv.)
HO
OH
O
O
DABCO (2 equiv.), CH2Cl2, rt, 5 min
O
O
3.2.1. Benzaldehyde diethyl acetal. 1H NMR 8CDCl3/
TMS, 250 MHz): dˆ7.40±7.44 8m, 2H), 7.25±7.33 8m,
3H), 5.48 8s, 1H), 3.44±3.55 8m, 4H), 1.19±1.27 8m, 6H);
13C NMR 8CDCl3/TMS, 63 MHz): dˆ138.99, 128.01,
127.91, 126.66, 100.95, 60.28, 15.24.
S
S
O
O
(3 equiv.), NBS (1 equiv.)
OH
DABCO (2 equiv.), CH2Cl2, rt, 5 min, 85%
HO
THPO
THPO
Scheme 2.

4516
B. Karimi et al. / Tetrahedron 58 ꢀ2002) 4513±4516
3.2.2. Acetophenone diethyl acetal. 1H NMR 8CDCl3/
TMS, 250 MHz): dˆ7.60±7.61 8m, 2H), 7.25±7.57 8m,
3H), 3.38±3.56 8m, 4H), 1.43 8s, 3H), 1.21±1.28 8m, 6H);
13C NMR 8CDCl3/TMS, 63 MHz): dˆ151.56, 135.62,
135.01, 133.81, 108.87, 64.29, 34.82, 22.66.
1.4 Hz, 1H), 7.56±7.59 8d, Jˆ8.4 Hz, 2H), 7.49±7.53 8t,
Jˆ7.4 Hz, 2H), 7.23±7.26 8dd, Jˆ8.4, 1.4 Hz, 2H), 5.54
8s, 1H), 4.27±4.30 8dd, Jˆ11.0, 3.6 Hz, 2H), 3.98±4.03
8pseudo-t, Jˆ11.0 Hz, 2H), 2.20±2.27 8tq, Jˆ5.0, 13.3 Hz,
1H), 1.44±1.48 8quind, Jˆ1.3, 13.3 Hz, 1H); 13C NMR
8125 MHz, CDCl3, 258C, TMS): dˆ165.08, 151.29,
136.58, 133.68, 130.25, 129.62, 128.65, 127.38, 121.55,
101.05, 67.45, 25.82.
3.2.3. 2,2-Diethoxy-4-phenylbutane. 1H NMR 8CDCl3/
TMS, 250 MHz): dˆ7.23±7.37 8m, 5H), 3.52±3.64 8m,
4H), 2.69±2.76 8m, 2H), 1.99±2.06 8m, 2H), 1.51 8s, 3H),
1.23±1.33 8m, 6H); 13C NMR 8CDCl3/TMS, 63 MHz):
dˆ142.62, 128.77, 128.65, 126.17, 101.59, 55.99, 39.56,
31.13, 22.56, 15.94.
Acknowledgements
The authors appreciate Institute for Advanced Studies in
Basic Sciences 8IASBS) Research Council for supportof
this work.
3.2.4. 2-)4-Chlorophenyl)-1,3-dioxane. 1H NMR 8250
MHz, CDCl3, 258C, TMS): dˆ7.40±7.49 8d, Jˆ8.0 Hz,
2H), dˆ7.30±7.34 8d, Jˆ8.0 Hz, 2H), dˆ5.44 8s, 1H),
dˆ4.20±4.26 8dd, Jˆ5.0, 11.3 Hz, 2H), dˆ3.88±3.98
8pseudo-t, Jˆ11.3 Hz, 2H), dˆ2.14±2.23 8tq, Jˆ5,
13.2 Hz, 1H), dˆ1.37±1.43 8quind, Jˆ1.2, 13.2 Hz, 1H);
13C NMR 863 MHz, CDCl3, 258C, TMS): dˆ137.70,
134.95, 128.81, 127.91, 101.19, 67.78, 26.09.
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3.66±3.78 8m, 4H), dˆ1.94±2.08 8tq, Jˆ5.4, 12.9 Hz,
1H), dˆ1.44 8s, 3H), dˆ1.11±1.19 8quind, Jˆ1.2, 12.9
Hz, 1H); 13C NMR 863 MHz, CDCl3, 258C, TMS): dˆ
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1
3.2.7. 2-Methyl-2-)2-phenylethyl)-1,3-dioxane. H NMR
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dˆ3.79±3.89 8m, 4H), dˆ2.73±2.79 8m, 2H), dˆ1.98±
2.05 8m, 2H), dˆ1.97±1.73 8m, 1H), dˆ1.48±1.68 8m,
1H), dˆ1.44 8s, 3H); 13C NMR 863 MHz, CDCl3, 258C,
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1.59±1.66 8m, 6H), dˆ1.16±1.26 8m, broad, 18H), 13C
NMR 863 MHz, CDCl3, 258C, TMS): dˆ100.77, 60.28,
60.03, 40.30 8two peaks), 36.50, 30.29 8seven peaks),
19.25 8two peaks).
3.2.9. 2-[3-)Tetrahydro-pyran-2-yloxy)-phenyl]-[1,3]-di-
oxane. 1H NMR 8500 MHz, CDCl3, 258C, TMS): dˆ
8.20±8.22 8dd, Jˆ8.4, 1.4 Hz, 2H), 7.61±7.65 8tt, Jˆ7.4,