Chemistry Letters 2002
11
Table 2. DBSA-catalyzed synthesis of thioethers in water
R1SR2
O
SH
+
HS
(1.1 equiv.)
Ph
H
10 mmol
R1SH
filtered then
S
S
Entry
R2OH (equiv.)
Ph3COH (1.0)
Ph
H
washed with H2O
CH3(CH2)11SH
CH3(CH2)11SH
97
93
1
2
(eq 2)
Ph2CHOH (2.0)
In summary, dehydration reactions such as etherification,
3a
4
BuO
(2.0)
87
82
thioetherification, and dithioacetalization are efficiently cata-
lyzed by DBSA in water. The present system has advantages such
as selectivity based on the difference in hydrophobicity and easy
work-up, and would lead to environmentally benign chemical
processes.
CH3(CH2)11SH
CH3(CH2)11SH
OH
OH
MeO
(1.0)
5b
6c
76
96
Ph3COH (1.0)
Ph3COH (1.0)
PhSH
This paper is dedicated to Professor Teruaki Mukaiyama on
the occasion of his 75th birthday and also in recognition of his
outstanding contributions to synthetic organic chemistry.
PhCH2SH
References and Notes
Table 3. DBSA-catalyzed dithioacetalization in watera
1
2
P. A. Grieco, ‘‘Organic Synthesis in Water,’’ Blacky Academic and
Professional, London (1998); C.-J. Li and T.-H. Chan, ‘‘Organic
Reactions in Aqueous Media,’’ John Wiley & Sons, New York (1997).
S. Kobayashi and T. Wakabayashi, Tetrahedron Lett., 39, 5389 (1998);
K. Manabe and S. Kobayashi, Synlett, 1999, 547; K. Manabe and S.
Kobayashi, Tetrahedron Lett., 40, 3773 (1999); S. Kobayashi, Y. Mori,
S. Nagayama, and K. Manabe, Green Chem., 1999, 175; K. Manabe, Y.
Mori, S. Nagayama, K. Odashima, and S. Kobayashi, Inorg. Chim. Acta
296, 158 (1999); K. Manabe, Y. Mori, and S. Kobayashi, Tetrahedron,
55, 11203 (1999); K. Manabe, Y. Mori, T. Wakabayashi, S. Nagayama,
and S. Kobayashi, J. Am. Chem. Soc., 122, 7202 (2000).
S. Kobayashi, T. Busujima, and S. Nagayama, Synlett, 1999, 545; K.
Manabe, Y. Mori, and S. Kobayashi, Synlett, 1999, 1401; K. Manabe
andS. Kobayashi, Org. Lett., 1, 1965(1999);K. Manabe, Y. Mori, andS.
Kobayashi, Tetrahedron, 57, 2537 (2001).
O
SH
S
R2
S
R1
+
R1
R2
HS
(1.0—1.1 equiv.)
Entry
Substrate
94
88
92
PhCHO
1
2b
3
PhCHO
3
4
CH3(CH2)4CHO
O
94 (95)c
82
4
S. Kobayashi, T. Busujima, and S. Nagayama, J. Chem. Soc., Chem.
Commun., 1998, 19; K. Manabe and S. Kobayashi, Chem. Commun.,
2000, 669; Y. Mori, K. Kakumoto, K. Manabe, and S. Kobayashi,
Tetrahedron Lett., 41, 3107 (2000); S. Kobayashi, W. W.-L. Lam, and
K. Manabe, Tetrahedron Lett., 41, 6115 (2000); K. Manabe, N.
Aoyama, and S. Kobayashi, Adv. Synth. Catal., 343, 174 (2001); Y.
Mori, K. Manabe, and S. Kobayashi, Angew. Chem., Int. Ed., 40, 2815
(2001).
Ph
H
O
5d
O
5
6
K. Manabe, X.-M. Sun, and S. Kobayashi, J. Am. Chem. Soc., 123,
10101 (2001).
A. W. Williamson, J. Chem. Soc., 4, 229 (1852); N. Baggett,
‘‘Comprehensive Organic Synthesis,’’ ed. by D. Barton and W. D.
Ollins, Pergaman, Oxford (1979), Vol. 1, p 77.
6d,e
74
7
For recent examples of acid-catalyzed etherification: G. V. M. Sharma
and A. K. Mahalingam, J. Org. Chem., 64, 8943 (1999); T. Ooi, H.
Ichikawa, Y. Itagaki, and K. Maruoka, Heterocycles, 52, 575 (2000); G.
V. M. Sharma, T. R. Prasad, and A. K. Mahalingam, Tetrahedron Lett.,
42, 759 (2001).
(entries 1-4). Furthermore, aliphatic or aromatic ketones also
reacted well to give the corresponding adducts in good yields
(entries 5 and 6). It is noteworthy that only 1 mol% of DBSA was
sufficient to catalyze the reaction without any difficulty in the case
of the substrate shown in entry 4.
8
9
Dodecylbenzenesulfonic acid (soft type) was purchased from Tokyo
Kasei Kogyo Co., Ltd.
Symmetric ethers derived from benzyl alcohols were also obtained as
by-products.
In addition, easy work-up has been realized without use of
organic solvents when the products are solid and insoluble in
water. In fact, the dithioacetalization of cinnamaldehyde on
10 mmol-scale with 1 mol% of DBSA proceeded smoothly to
deposit crystals. Pure product was obtained inexcellent yield after
the crystals were filtered and washed with water (eq 2). This
simple procedure is one of the advantages of the present reaction
system.
10 The log Poct value: dodecanol (5.13), propanol (0.25). M. H. Abraham,
H. S. Chadha, G. S. Whiting, and R. C. Mitchell, J. Pharm. Sci., 83, 1085
(1994).
11 T. W. Greene and P. G. M. Wuts, ‘‘Protective Groups in Organic
Synthesis,’’ 3rd ed., Wiley, New York (1999).
12 For examples of acid-catalyzed thioetherification: J. J. Pastuszak and A.
Chimiak, J. Org. Chem., 46, 1868(1981);R. Breitschuhand D. Seebach,
Synthesis, 1992, 83.
13 M. A. Ceschi, L. A. Felix, and C. Peppe, Tetrahedron Lett., 41, 9695
(2000).