2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO), N-bromosuccinimide (NBS) and bromine as efficient catalysts for dithioacetalization and oxathioacetalization of carbonyl compounds and transdithioacetalization reactions

Article abstract of DOI:10.1080/10426500211712

The use of 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TABCO), N-bromosuccinimide (NBS), and bromine as efficient catalysts for conversion of carbonyl compounds to their cyclic and acyclic dithioacetals and 1,3-oxathiolanes under mild reaction conditions are described. These catalysts are also used for efficient transdithioacetalization of acetals, diacetals, ketals, acylals, enamines, hydrazones, and oximes with high yields in the presence of thiols.

Full text of DOI:10.1080/10426500211712

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO),
N-Bromosuccinimide (NBS) and Bromine as
Efficient Catalysts for Dithioacetalization and
Oxathioacetalization of Carbonyl Compounds and
Transdithioacetalization Reactions
Nasser Iranpoor , Habib Firouzabadi , Hamid Reza Shaterian & M. A. Zolfigol
To cite this article: Nasser Iranpoor , Habib Firouzabadi , Hamid Reza Shaterian & M. A. Zolfigol
(2002) 2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO), N-Bromosuccinimide (NBS) and
Bromine as Efficient Catalysts for Dithioacetalization and Oxathioacetalization of Carbonyl
Compounds and Transdithioacetalization Reactions, Phosphorus, Sulfur, and Silicon and the
Related Elements, 177:5, 1047-1071, DOI: 10.1080/10426500211712
To link to this article: http://dx.doi.org/10.1080/10426500211712
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Date: 09 October 2015, At: 07:04

Phosphorus, Sulfur and Silicon, 2002, Vol. 177:1047–1071
C
Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290092334
2,4,4,6-TETRABROMO-2,5-CYCLOHEXADIENONE
(TABCO), N-BROMOSUCCINIMIDE (NBS) AND
BROMINE AS EFFICIENT CATALYSTS FOR
DITHIOACETALIZATION AND
OXATHIOACETALIZATION OF CARBONYL
COMPOUNDS AND TRANSDITHIOACETALIZATION
REACTIONS
Nasser Iranpoor, Habib Firouzabadi, Hamid Reza Shaterian,
and M. A. Zolfigol
Department of Chemistry, Shiraz University, Shiraz, Iran
(Received June 20, 2001; accepted November 3, 2001)
The use of 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TABCO), N-
bromosuccinimide (NBS), and bromine as efficient catalysts for conver-
sion of carbonyl compounds to their cyclic and acyclic dithioacetals and
1,3-oxathiolanes under mild reaction conditions are described. These
catalysts are also used for efficient transdithioacetalization of acetals,
diacetals, ketals, acylals, enamines, hydrazones, and oximes with high
yields in the presence of thiols.
Keywords: 1,3-Oxathiolane; 2,4,4,6-tetrabromo-2,5-cyclohexadienone
(TABCO); bromine; carbonyl compound; dithioacetalization; N-
bromosuccinimide (NBS); thiol; transdithioacetalization
INTRODUCTION
The protection of organic compounds is an important goal in multistep
organic synthesis.1 Due to the resistance of thioacetals toward hy-
drolytic cleavage under ordinary acidic and basic conditions, the protec-
tion of carbonyl groups as their cyclic and acyclic dithioacetals has at-
tracted organic chemists.2 Cyclic S,S-acetals for example, 1,3-dithianes
Present address: Bu-Ali Sina University, Hamedan, Iran.
This article is dedicated to Professor Ahmad Banihashemi on the occasion of his
70th birthday.
The authors are thankful to the Shiraz University Research Council for the partial
support of this work.
Address correspondence to N. Iranpoor, Department of Chemistry, Shiraz University,
Shiraz 71454, Iran. E-mail: iranpoor@chem.susc.ac.ir
1047

1048
N. Iranpoor et al.
and 1,3-dithiolanes, also have found wide synthetic uses as precursors
of acyl anion equivalents and as masked methylene group in organic
7
synthesis.3
Dithioacetals can be prepared by condensation of carbonyl com-
pounds and thiols or dithiols in the presence of protic acids, Lewis
36
acids, and some silicon reagents.3
Some of the reported methods
suffer from: 1) long reaction times, 2) stoichiometric use of expensive
reagents, and 3) low selectivity when applied to the mixture of aldehy-
des and ketones.
Recently, transdithioacetalization of acetals has gained favor as
alternative method for the preparation of dithioacetals, in which
catalysts such as BF3.OEt2,37 Bui2AlS(CH2)2SAlBui2,38 and CoCl2,
Me3SiCl39 have been employed. This interesting transformation was
later extended to transdithioacetalization of ketals, oxathioacetals and
oxathioketals by Envirocat EPZ10R, 40 and also to ketals, oximes, enam-
ines and tosylhydrazones using natural kaolinitic clay.41 However, since
most of these catalysts work under reflux conditions and some of them
are not easily available,40,41 introducing of cheap, easily available, se-
lective, and efficient catalysts is always welcome by synthetic organic
chemists.
In continuation of our recent works on dithioacetalization of car-
36
bonyl compounds and transdithioacetalization reactions,34
we now
introduce compounds that they potentially carry positive halonium
ions and can be used as efficient catalysts for both dithioacetalization
and transdithioacetalization reactions. The compounds we have
used for this purpose are: 2,4,4,6-tetrabromo-2,5-cyclohexadienone
47
(TABCO),42
N-bromosuccinimide (NBS) and molecular bromine
(Br2). We have employed them as efficient and chemoselective catalysts
for the conversion of aldehydes and ketones to their corresponding
cyclic and acyclic dithioacetals and also 1,3-oxathiolanes under mild
reaction conditions. The transdithioacetalization of acetals, diacetals,
ketals, acylals, imines, enamines, and hydrazones in CHCl3 at room
temperature and oximes under reflux condition were also performed
in the presence of these catalysts.
RESULTS AND DISCUSSION
Various types of aromatic aldehydes with electron-donating and
electron-withdrawing groups, cinnamaldehyde and aliphatic aldehy-
des were converted to their cyclic S,S-acetals with HS(CH2)nSH, n = 2,
3 in the presence of TABCO (Method A, Table I), NBS (Method B,
Table II) or Br2 (Method C, Table II) as catalysts, with excellent yields

Transdithioacetalization Reactions
1049
TABLE I Dithioacetalization of Carbonyl Compounds with HS(CH2)nSH
Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO, Method A)
in CHCl3 at Room Temperature
Entry
1
Substrate
n
Sub/thiol/cat
Time (min)
Yielda (%)
2
3
1/1.5/0.2
1/1.5/0.3
10
3
94
95
2
3
4
5
6
7
8
2
3
1/1.5/0.2
1/1.5/0.3
8
3
95
93
2
3
1/1.5/0.2
1/1.5/0.3
15
3
93
92
2
3
1/1.5/0.3
1/1.5/0.3
8
6
91
90
2
3
1/1.5/0.2
1/1.5/0.2
18
15
92
92
2
3
1/1.5/0.2
1/1.5/0.3
20
6
94
95
2
3
1/1.5/0.2
1/1.5/0.2
5
4
96
96
2
3
1/1.5/0.2
1/1.5/0.3
25
5
92
93
9
2
3
1/1.5/0.2
1/1.5/0.3
7
3
94
95
10
2
3
1/2.0/0.3
1/2.0/0.4
45
25
89
90
11
12
2
3
1/2.0/0.4
1/2.0/0.4
180
150
85
84
2
3
1/2.0/0.4
1/2.0/0.4
100
80
89
89
2
3
1/1.5/0.3
1/1.5/0.3
25
15
92
93
13
14
2
3
1/1.5/0.3
1/1.5/0.4
80
50
90
91
(Continued on next page)

1050
N. Iranpoor et al.
TABLE I Dithioacetalization of Carbonyl Compounds with HS(CH2)nSH
Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO, Method A) in
CHCl3 at Room Temperature (Continued)
Entry
15
Substrate
n
Sub/thiol/cat Time (min) Yielda (%)
2
3
1/1.5/0.3
1/1.5/0.4
90
45
90
92
16
2
3
1/1.5/0.3
1/1.5/0.4
40
30
91
90
17
2
3
1/2.0/0.4
1/2.5/0.4
180
140
87
87
2
3
1/2.5/0.4
1/2.5/0.5
240
200
82
75
18
aIsolated yield.
at room temperature. We have also investigated the protection of car-
bonyl groups of various aromatic, aliphatic and steroidal ketones in the
presence of these catalysts at room temperature (Scheme 1).
SCHEME 1
We observed that dithioacetalization of ketones with these catalysts
proceeded very smoothly and cleanly with excellent yields but with
longer reaction times in comparison with aldehydes (Tables I and II).

TABLE II Dithioacetalization of Carbonyl Compounds with HS(CH2)nSH
Catalyzed by N-Bromosuccinimide (NBS, Method B) Bromine (Br2, Method C)
in CHCl3 at Room Temperature
Entry
1
Substrate
n
Sub/thiol/cat, method
Time (min)
Yielda (%)
2
3
1/1.5/0.2, B
1/1.5/0.1, C
5
4
96
95
2
3
1/1.5/0.2, B
1/1.5/0.1, C
6
3
97
96
2
3
4
5
2
3
1/1.5/0.2, B
1/1.5/0.1, C
9
15
95
96
2
3
1/1.5/0.2, B
1/1.5/0.1, C
5
4
96
96
2
3
1/1.5/0.2, B
1/1.5/0.1, C
15
20
94
93
2
3
1/1.5/0.2, B
1/1.5/0.1, C
4
4
94
90
6
7
2
3
1/1.5/0.2, B
1/1.5/0.1, C
5
4
94
92
2
3
1/2.0/0.3, B
1/2.0/0.2, C
45
50
90
91
8
2
3
1/2.5/0.4, B
1/2.5/0.4, C
170
160
87
85
9
2
3
1/2.0/0.4, B
1/2.0/0.3, C
80
90
90
89
10
2
3
1/1.5/0.3, B
1/1.5/0.2, C
15
10
92
91
11
12
2
3
1/1.5/0.3, B
1/1.5/0.2, C
70
80
90
86
2
3
1/2.0/0.4, B
1/2.0/0.2, C
80
55
90
89
13
14
2
3
1/1.5/0.2, B
1/1.5/0.2, C
30
35
87
85
2
3
1/2.5/0.4, B
1/2.5/0.4, C
170
140
83
82
15
aIsolated yield.

1052
N. Iranpoor et al.
We also studied the possibility of dithioacetalization of carbonyl com-
pounds to their corresponding acyclic dithioacetals with benzylthiol,
1-butanethiol, and ethylthiol catalyzed by all these catalysts. The reac-
tions were occurred at room temperature and acyclic dithioacetals were
obtained in excellent yields (Table III).
TABLE III Dithioacetalization of Carbonyl Compounds with Benzylthiol,
1-Butylthiol and Ethylthiol Catalyzed by 2,4,4,6-Tetrabromo-
2,5-cyclohexadienone (TABCO, Method A), N-Bromosuccinimide (NBS,
Method B) and Bromine (Br2, Method C) in CHCl3 at Room Temperature
Subs/thiol/ Time Yielda
Entry
1
Substrate
Product
Thiol
cat, method (min) (%)
PhCH2SH
1/2.5/0.2, A
1/2.5/0.1, B
1/2.5/0.2, C
5
4
5
95
97
96
2
3
PhCH2SH
1/2.5/0.2, A
1/2.5/0.1, B
1/2.5/0.2, C
5
4
5
95
98
96
CH3(CH2)3SH 1/2.5/0.2, A
1/2.5/0.1, B
5
5
5
95
95
96
1/2.5/0.2, C
4
5
CH3CH2SH 1/2.5/0.2, A
1/2.5/0.1, B
6
5
6
95
97
96
1/2.5/0.2, C
PhCH2SH
1/3.0/0.3, A 45
1/3.0/0.2, B 40
1/3.0/0.3, C 45
92
93
91
6
7
CH3CH2SH 1/3.0/0.3, A 12
1/3.0/0.2, B 15
91
92
91
1/3.0/0.3, C 20
PhCH2SH
1/3.0/0.4, A 75
1/3.0/0.2, B 65
1/3.0/0.3, C 80
90
91
92
8
CH3(CH2)3SH 1/3.0/0.4, A 75
1/3.0/0.2, B 60
92
92
91
1/3.0/0.3, C 70
aIsolated yield.

Transdithioacetalization Reactions
1053
In order to show the ability of TABCO, NBS, and Br2 to act as selec-
tive catalysts, we studied dithioacetalization of aldehydes and ketones
with 1,3-propanedithiol in binary mixtures. By these methods, ben-
zaldehyde was protected in the presence of 4-nitrobenzaldehyde with
the ratio of 95:5. 4-Methylbenzaldehyde was protected in the presence
of benzaldehyde with the ratio of 85:15. Benzaldehyde in the presence
of acetophenone was exclusively protected. Acetophenone was quanti-
tatively converted to its S,S-acetal whereas, benzophenone remained
almost intact. The results of these selective protections are shown in
Table IV.
1,3-Oxathiolanes are considerably more stable than the corre-
sponding O,O-acetals, and ketals under acidic conditions and in
comparison with S,S-acetals and ketals are more easily deprotected.1
To extend the synthetic applications of the reaction, we stud-
ied 1,3-oxathioacetalization of different carbonyl groups with
2-mercaptoethanol catalyzed by TABCO. 1,3-Oxathiolanes were
obtained from the reaction of aldehydes and ketones with
2-mercaptoethanol at room temperature in high yields when TABCO
was used as a catalyst in CHCl3 (Table V). Similarly, NBS and Br2
showed to be efficient catalysts for this transformation at room
temperature.
We continued this study by investigating the possibility of us-
ing these catalysts for transdithioacetalization reaction of different
protected compounds of carbonyl groups (Scheme 2). These reactions
are especially interesting since O,O-acetals are generally more reactive
than their corresponding carbonyl compounds in the dithioacetalization
reactions and give efficiently the desired product at short reaction time
with excellent yield. Various types of diethyl acetals and ketals were
converted to their cyclic 1,3-dithioacetals (Table VI, entries 1–7, 11, 14,
15, 17, 18) and also to their acyclic dithioacetals (Table VI, entries 13,
SCHEME 2

1054
N. Iranpoor et al.
TABLE IV Selective Dithioacetalization of Carbonyl Compounds with
HS(CH2)3SH Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO,
Method A), N-Bromosuccinimide (NBS, Method B) and Bromine
(Br2, Method C) in CHCl3 at Room Temperature
Substrate 1
Substrate 2
Product 1
Product 2
Sub 1/sub 2/thiol/ Time Yielda
Entry
1
cat, method
(min)
(%)
1/1/1.5/0.2, A
5
95
5
1/1/1.5/0.2, A
3
85
2
15
1/1/1.5/0.2, A
1/1/1.5/0.1, B
1/1/2.0/0.2, B
5
5
100
3
4
0
100
0
5
40
100
0

Transdithioacetalization Reactions
1055
TABLE IV Selective Dithioacetalization of Carbonyl Compounds with
HS(CH2)3SH Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO,
Method A), N-Bromosuccinimide (NBS, Method B) and Bromine
(Br2, Method C) in CHCl3 at Room Temperature (Continued)
Substrate 1
Substrate 2
Product 1
Product 2
Sub 1/sub 2/thiol/ Time Yielda
Entry
6
cat, method
(min) (%)
1/1/2.0/0.3, C
50
100
0
7
1/1/1.5/0.2, C
5
100
0
aYield based on GC and NMR analysis.
16, 19) in short reaction times in the presence of catalytic amounts of
TABCO in high to excellent yields. Similarly, NBS and Br2 showed to be
efficient catalysts for this transformation at room temperature. By the
use of these catalysts, the sterically hindered benzophenone diethylac-
etal was also converted to its corresponding 2,2-diphenyl-1,3-dithiolane
in good yield at room temperature (Table VI, entry 17). We also have
performed the conversion of acetals and ketals to their corresponding
1,3-oxathiolanes with 2-mercaptoethanol in excellent yields in the pres-
ence of TABCO, NBS and Br2 at room temperature. This transformation
was performed in the presence of 0.1 mmol of either catalyst for acetals
(Table VI, entries 8–10) and 0.3 mmol of the catalyst for ketals at room
temperature (Table VI, entry 12).
Transdithioacetalization of 1,3-dioxanes (Table VII, entries 1–5 and
15–18) and 1,3-dioxolanes (Table VII, entries 6–14) with HS(CH2)3SH
were also studied in the presence of these catalysts. The results
obtained using TABCO as catalyst in these reactions are represented
in the Table VII. The reactions proceeded well at room temperature
and the corresponding 1,3-dithianes were obtained in high to excellent
yields.
Diacetals of [2,2-bis(hydroxymethyl)-1,3-propanediol] are stable cry-
stalline derivatives of aldehydes and ketones which their handling is

TABLE V Preparation of 1,3-Oxathiolanes from Carbonyl Compounds with
2-Mercaptoethanol Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone
(TABCO) in CHCl3 at Room Temperature
Entry
1
Substrate
Product
Sub/thiol/cat Time (min) Yielda (%)
1/1.5/0.2
1/1.5/0.2
1/1.5/0.2
1/1.5/0.2
1/1.5/0.2
1/1.5/0.2
1/1.5/0.2
1/2.0/0.4
8
10
12
5
89
87
86
88
89
86
87
85
2
3
4
5
6
7
8
5
15
5
20
9
1/1.5/0.2
1/2.0/0.4
25
30
84
82
10
11
1/2.5/0.5
160
77
12
13
1/2.0/0.4
1/2.0/0.4
70
80
85
83
aIsolated yield.

Transdithioacetalization Reactions
1057
TABLE VI Transdithioacetalization of Diethyl Acetals and Ketals with
Thiols, Dithiols, and 2-Mercaptoethanol Catalyzed by 2,4,4,6-Tetrabromo-
2,5-cyclohexadienone (TABCO) in CHCl3 at Room Temperature
Sub/thiol/ Time Yielda
cat (min) (%)
Entry
1
Substrate
Product
Thiol
HS(CH2)3SH 1/1.5/0.1
HS(CH2)3SH 1/1.5/0.1
HS(CH2)3SH 1/1.5/0.1
HS(CH2)3SH 1/1.5/0.1
HS(CH2)3SH 1/1.5/0.1
HS(CH2)2SH 1/1.5/0.1
HS(CH2)2SH 1/1.5/0.1
HS(CH2)2OH 1/1.5/0.1
10
25
15
10
5
91
90
91
93
94
90
91
90
2
3
4
5
6
7
8
12
15
35
9
10
11
HS(CH2)2OH 1/1.5/0.1
HS(CH2)2OH 1/1.5/0.1
HS(CH2)2SH 1/2.0/0.3
10
15
40
90
90
88
(Continued on next page)

1058
N. Iranpoor et al.
TABLE VI Transdithioacetalization of Diethyl Acetals and Ketals with
Thiols, Dithiols, and 2-Mercaptoethanol Catalyzed by 2,4,4,6-Tetrabromo-
2,5-cyclohexadienone (TABCO) in CHCl3 at Room Temperature (Continued)
Sub/thiol/ Time Yielda
Entry
12
Substrate
Product
Thiol
cat
(min) (%)
HS(CH2)2OH 1/2.0/0.3
35
45
89
90
13
PhCH2SH
1/3.0/0.3
14
15
16
HS(CH2)3SH 1/1.5/0.2
HS(CH2)3SH 1/1.5/0.2
CH3CH2SH 1/3.0/0.2
25
20
35
91
91
89
17
HS(CH2)2SH 1/2.5/0.5 100
75
18
19
HS(CH2)3SH 1/2.0/0.3
CH3(CH2)3SH 1/3.0/0.3
80
85
90
87
aIsolated yield.
easy.50,51 We studied the possibility of their transdithioacetalization
with HS(CH2)3SH in the presence of TABCO, NBS, and Br2 as cata-
lyst. The reactions were completed within short reaction times (10–25
min) and excellent yields of 1,3-dithianes (90–94%) were obtained. The

Transdithioacetalization Reactions
1059
TABLE VII Transdithioacetalization of 1,3-Dioxanes and 1,3-Dioxolanes
with HS(CH2)3SH Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone
(TABCO) in CHCl3 at Room Temperature
Sub/thiol/ Time Yielda
Entry
1
Substrate
Product
cat
(min)
(%)
1/1.5/0.1
8
92
2
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
1/2.0/0.3
15
20
15
10
12
20
12
8
93
90
94
87
90
90
92
91
80
3
4
5
6
7
8
9
10
5
11
1/2.0/0.3
60
75
(Continued on next page)

1060
N. Iranpoor et al.
TABLE VII Transdithioacetalization of 1,3-Dioxanes and 1,3-Dioxolanes
with HS(CH2)3SH Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone
(TABCO) in CHCl3 at Room Temperature (Continued)
Sub/thiol/ Time Yielda
Entry
12
Substrate
Product
cat
(min)
(%)
1/2.0/0.3
60
84
13
1/1.5/0.2
1/1.5/0.2
1/1.5/0.2
25
15
30
89
90
89
14
15
16
1/2.0/0.4
120
82
17
18
1/2.0/0.3
1/2.0/0.3
50
65
87
89
aIsolated yield.
results obtained using NBS as representative catalyst are shown in the
Table VIII.
By use of these catalysts, acylals (geminal diacetates), [Scheme,
X = (OAc)2, R0 = H], as stable derivatives of aldehydes were also
converted to their corresponding 1,3-dithianes with HS(CH2)3SH
in high yields and short reaction times (5–18 min). The results
obtained in the presence of NBS as catalyst are shown in the
Table IX.

TABLE VIII Transdithioacetalization of Cyclic Diacetals with HS(CH2)3SH
Catalyzed by N-Bromosuccinimide (NBS) in CHCl3 at Room Temperature
Sub/thiol/ Time Yielda
Entry
1
Substrate
Product
cat
(min)
(%)
1/2.5/0.15
10
90
2
3
1/2.5/0.2
1/2.5/0.2
1/2.5/0.2
1/2.5/0.1
20
25
18
10
90
91
92
94
4
5
1/2.5/0.1
1/2.5/0.1
15
12
91
92
6
7
1/2.5/0.2
1/2.5/0.2
25
10
90
94
8
9
10
1/2.5/0.1
1/3.0/0.2
15
25
90
90
11
aIsolated yield.

1062
N. Iranpoor et al.
TABLE IX Transdithioacetalization of Acytals with HS(CH2)3SH Catalyzed
by N-Bromosuccinimide (NBS) in CHCl3 at Room Temperature
Sub/thiol/ Time Yielda
Entry
1
Substrate
Product
cat
(min)
(%)
1/1.5/0.1
5
94
2
3
4
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
10
10
15
95
93
93
1/1.5/0.1
1/1.5/0.1
12
10
90
90
5
6
1/1.5/0.1
1/1.5/0.1
12
10
93
90
7
8
1/1.5/0.1
1/1.5/0.1
18
15
91
90
9
10
aIsolated yield.

Transdithioacetalization Reactions
1063
Aldehydes and ketones are generally purified and characterized via
their corresponding crystalline oximes or hydrazones that may be em-
ployed for further synthetic manipulation. Therefore, in-situ prepara-
tion of dithioacetals from oximes and hydrazones is a useful synthetic
transformation. In the process of in-situ conversion of benzaldehyde
oxime to its 1,3-dithiane with HS(CH2)3SH and TABCO, NBS and
Br2 as catalysts (0.2 molar equivalent), it was observed that these
catalysts are not efficient for this transformation at room tempera-
ture. For example, in the case of Br2 which is more efficient than the
other two catalysts, benzaldehyde oxime was converted to 2-phenyl-
1,3-dithiane only in 55% yield after 48 h at room temperature. We
therefore performed the transdithioacetalization of oximes under re-
flux condition in the presence of Br2 as catalyst. Both aldoximes and
ketoximes reacted under reflux condition with 1,3-propanedithiol and
furnished their corresponding 1,3-dithianes (Table X). In comparison
with kaolinitic clay, which was not able, to convert acetophenone oxime
to its dithioacetals in refluxing CCl4 (0% yield is reported)41 with
this method, the reaction produces 2-methyl-2-phenyl-1,3-dithiane in
70% yield.
In comparison with the reaction of oximes, TABCO, NBS, and Br2
were found to have similar efficiency for transdithioacetalization of hy-
drazones, imines and enamines. We studied transdithioacetalization of
imines and enamines with HS(CH2)3SH in the presence of Br2 as a
representative catalyst. Conversion of these compounds to their corre-
sponding 1,3-dithiane was occurred at room temperature with excellent
yields (Table XI, entries 1–7). We also extended our studies for trans-
dithioacetalization of phenylhydrazones of both aldehydes and ketones
with Br2 as catalyst in the presence of HS(CH2)3SH. The reactions
were occurred at room temperature and produced the corresponding
1,3-dithianes in high yields (Table XI, entries 8, 9).
In order to study the chemoselectivity of these catalysts, different
binary mixtures were selected and their competitive reactions with
HS(CH2)3SH were studied. Very high chemoselectivity behavior of
TABCO, NBS, and Br2 for transdithioacetalization reactions has been
noticed. By this method, benzaldehyde diacetate was exclusively con-
verted to its 1,3-dithiane in the presence of acetophenone (Table XII,
entry 1). 4-methyl acetophenone diethyl acetal was quantitatively con-
verted to its 1,3-dithiane in the presence of 4-methyl acetophenone
(Table XII, entry 2). Excellent chemoselectivity in the transdithioac-
etalization of binary mixtures such as benzaldehyde diethyl acetal
and benzaldehyde diacetate (Table XII, entry 3), 4-chlorobenzaldeyde
diethyl acetal and 4-chlorobenzaldehyde diacetate (Table XII, entry 4),
2-methyl-2-(4-chlorophenyl)-1,3-dioxolane and 4-chlorobenzaldehyde

1064
N. Iranpoor et al.
TABLE X Transdithioacetalization of Oximes with HS(CH2)3SH Catalyzed
by Bromine (Br2) in CHCl3 Under Reflux Conditions
Sub/thiol/ Time Yielda
Entry
1
Substrate
Product
cat
(min)
(%)
1/5.0/0.8
10
90
2
3
1/5.0/0.8
1/5.0/0.8
1/5.0/0.8
1/5.0/0.8
1/5.0/0.8
1/5.0/0.8
1/5.0/0.8
1/5.0/0.8
1/5.0/0.8
11.5
12
11
9
89
87
89
92
90
91
85
89
85
4
5
6
10
8
7
75
10
15
8
9
10
11
12
1/7.0/1.0
24
48
70
50
1/10.0/2.0
aIsolated yield.

Transdithioacetalization Reactions
1065
TABLE XI Transdithioacetalization of Imines, Enamines, and
Phenylhydrazones with HS(CH2)3SH Catalyzed by Bromine (Br2) in CHCl3
at Room Temperature
Sub/thiol/ Time Yielda
Entry
1
Substrate
Product
cat
(h)
(%)
1/1.5/0.1
8
93
2
3
1/1.5/0.1
1/1.5/0.1
5
5
95
95
4
5
6
1/1.5/0.1
1/1.5/0.1
1/1.5/0.1
15
12
10
91
92
90
1/1.5/0.1
8
90
7
1/1.5/0.1
1/1.5/0.1
12
10
93
90
8
9
aIsolated yield.

1066
N. Iranpoor et al.
TABLE XII Selective Dithioacetalization of Carbonyl Compounds with
HS(CH2)3SH Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO,
Method A), N-Bromosuccinimide(NBS, Method B) and Bromine (Br2,
Method C) in CHCl3 at Room Temperature
Substrate 1
Substrate 2
Product 1
Product 2
Sub 1/sub 2/thiol/ Time Yielda
Entry
1
cat, method
(min), [h] (%)
1/1/1.5/0.2, A
(5)
100
0
1/1/1.5/0.1, B
(12)
100
0
2
3
4
5
6
1/1/1.5/0.2, C
1/1/1.5/0.2, A
1/1/1.5/0.2, A
1/1/1.5/0.2, A
(5)
(7)
(5)
(5)
100
0
100
0
100
0
100
0

Transdithioacetalization Reactions
1067
TABLE XII Selective Dithioacetalization of Carbonyl Compounds with
HS(CH2)3SH Catalyzed by 2,4,4,6-Tetrabromo-2,5-cyclohexadienone (TABCO,
Method A), N-Bromosuccinimide(NBS, Method B) and Bromine (Br2,
Method C) in CHCl3 at Room Temperature (Continued)
Substrate 1
Substrate 2
Product 1
Product 2
Sub 1/sub 2/thiol/
cat, method
Time
(min), [h] (%)
Yielda
Entry
7
1/1/1.5/0.2, C
(5)
100
0
8
1/1/3.0/0.4, C
[3]
90
10
85
9
1/1/3.0/0.4, C
1/1/3.0/0.4, C
[3]
[3]
15
10
75
25
aYields based on NMR and GC (n-heptane was used as internal standard).
diacetate (Table XII, entry 5), and 4-methylbenzaldehyde diacetate and
its 1,3-oxathiolane (Table XII, entry 6) was observed. We also observed
excellent chemoselectivity for dithioacetalization of aldehydes and ke-
tones in the presence of oximes and hydrazones. Benzaldehyde was
exclusively converted to 2-phenyl-1,3-dithiane with 1,3-propanedithiol
in the presence of benzaldoxime (Table XII, entry 7). Acetophenone was
transformed to 2-methyl-2-phenyl-1,3-dithiane in the presence of ben-
zaldoxime with the ratio of 90/10 after 3h (Table XII, entry 8). Benzalde-
hyde phenylthydrazone was converted to its 2-phenyl-1,3-dithiane in
the presence of acetophenone with the ratio of 85:15 (Table XII, entry 9).

1068
N. Iranpoor et al.
Benzaldehyde phenylhydrazone was also reacted in the presence
of benzaldoxime with the ratio of 75:25 after 3 h (Table XII, entry 10). As
it was observed in the competitive transdithioacetalization reactions,
oximes are less reactive than their carbonyl compounds or hydrazones
derivatives.
The mechanism of the reaction is not very clear to us. In our stud-
ies for acetalization of carbonyl compounds, we observed that NBS,
TABCO, and Br2 could act as efficient catalysts. Since in these reactions
no HBr is produced, it could be concluded that the catalytic activity of
these compounds could well be attributed to the presence of electrophilic
bromine in the reaction. Similarly in the case of dithioacetalization and
transdithioacetalization reactions, these compounds can act as source
of electrophilic halogen, however, the catalytic action of anhydrous
HBr produced through coupling of some thiol to disulfide cannot be
ruled out.
CONCLUSION
In conclusion, the presented catalysts are efficient, mild, readily avail-
able, and cheap for the protection of carbonyl compounds as their
cyclic S,S-acetal and ketals, acyclic S,S-acetals and ketals and 1,3-
oxathiolanes in high yields. The use of NBS and TABCO is advanta-
geous over molecular bromine due to ease of handling and safety as-
pects. Transdithioacetalization of a wide range of compounds such as
acetals, ketals, diacetals, acylals, imines, enamines, and hydrazones
can also be performed with these catalysts at room temperature. In
addition, the excellent chemoselectivity observed for dithioacetaliza-
tion of carbonyl compounds and transdithioacetalization of different
functionalities makes this method a useful contribution in organic
synthesis.
EXPERIMENTAL
General
All yields refer to isolated products unless otherwise stated. The prod-
ucts were identified by comparison of their physical and spectral data
(IR and NMR) with those obtained for known samples. The purity of the
products was determined with TLC on silica-gel polygram SIL G/UV
254 plates or GC analysis. IR spectra were recorded on a Perkin-Elmer
781 spectrophotometer. The NMR spectra were recorded on a Bruker
Avance DPX instrument (250 MHz).

Transdithioacetalization Reactions
1069
General Procedure for Dithioacetalization of Carbonyl
Compounds with TABCO, NBS, or Br2 as Catalyst
in CHCl3 at Room Temperature
To a solution of carbonyl compound (1 mmol) and the appropriate cat-
alysts (Tables I–III) in CHCl3 (5 mL), thiol or dithiol (Tables I–III) was
added at room temperature. The reaction mixture was stirred for the
appropriate time. The progress of the reaction was monitored by TLC
or GC. After completion of the reaction, an aqueous solution of NaOH
(5%, 25 mL) was added and the mixture was extracted with CHCl3
(3 25 mL). The organic layer was then separated and washed with
saturated solution of NaCl (20 mL) followed by H2O (20 mL). The or-
ganic layer was separated and dried over anhydrous Na2SO4. Removal
of the solvent gave almost pure cyclic and acyclic S,S-acetals and ketals
in excellent yields (Tables I–III). Further purification, if necessary, was
performed by column chromatography on a short column of silica gel
using petroleum ether (40–60 C)/ethyl acetate (9:1) as eluent. Products
were characterized by spectroscopic (1H NMR, 13C NMR, IR, MS) analy-
sis and also by comparison with the known samples prepared according
36
to the literature.3
General Procedure for Oxathioacetalization of Carbonyl
Compounds with TABCO as Catalyst in CHCl3
To a solution of carbonyl compound (1 mmol) and TABCO as catalyst
(Table V) in CHCl3 (5 mL), 2-mercaptoethanol was added at room tem-
perature. The reaction mixture was stirred for the appropriate time.
The progress of the reaction was monitored by TLC or GC. After com-
pletion of the reaction, an aqueous solution of NaOH (5%, 25 mL) was
added and the mixture was extracted with CHCl3 (3
25 mL). The
organic layer was then separated and washed with saturated solution
of NaCl (20 mL) followed by H2O (20 ml). The organic layer was sep-
arated and dried over anhydrous Na2SO4. Purification was performed
by vacuum distillation to afford desired product in good yield (Table V).
Products were characterized by spectroscopic (1H NMR, 13C NMR, IR,
MS) analysis and also by comparison with the known samples prepared
according to the literature.48,49
General Procedure for Transdithioacetalization
of Acetals, Diacetals, Ketals, Acylals, Enamines, Imines,
Hydrazones and Oximes Catalyzed by TABCO, NBS, or Br2
To a solution of acetal, ketal, acylal, enamine, imine, phenylhydra-
zone, or oximes (1 mmol) and thiol or dithiol (Tables VI–XI) in CHCl3
(5 mL), the appropriate catalyst (TABCO, NBS, or Br2) was added and
the mixture was stirred at room temperature for the appropriate time

1070
N. Iranpoor et al.
(Tables VI–IX, XI). The reaction of oximes was carried out under reflux
condition (Table X). TLC or GC monitored the progress of the reaction.
After completion of the reaction, aqueous solution of NaOH (5%, 25 mL)
was added and the mixture was extracted with CHCl3 (3
25 mL).
The organic layer was then separated and washed with saturated so-
lution of NaCl (20 mL) followed by H2O (20 mL). The organic phase
was dried over anhydrous Na2SO4. Purification was performed by col-
umn chromatography on silica gel and petroleum ether (40–60 C)/ethyl
acetate (9:1) was used as eluent. Products were characterized by com-
parison of their spectral data with samples prepared according to the
36
literature.3
General Procedure for Transoxathioacetalization
of Acetals and Ketals with TABCO as Catalyst
in Chloroform
To a solution of acetals and ketals (1 mmol) and TABCO (0.1–
0.3 mmol) in CHCl3 (5 mL), 2-mercaptoethanol was added at room
temperature (Table VI, entries 8–10, 12). The reaction mixture was
stirred for the appropriate time. The progress of the reaction was mon-
itored by TLC or GC. After completion of the reaction, aqueous solution
of NaOH (5%, 25 mL) was added and the mixture was extracted with
CHCl3 (3 25 mL). The organic layer was then separated and washed
with saturated solution of NaCl (20 mL) followed by H2O (20 mL). The
organic phase was dried over anhydrous Na2SO4. Purification was per-
formed by vacuum distillation to afford the desired products in high
yield. Products were characterized by comparison of their spectral data
with those of samples prepared according to the literature.48,49
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