Highly efficient dithioacetalization of carbonyl compounds catalyzed with iodine supported on neutral alumina

Article abstract of DOI:10.1246/cl.2001.794

Aldehydes and ketones are protected as their corresponding dithioacetals with ethane-1,2-dithiol in the presence of a catalytic amount of iodine supported on neutral alumina surface. This is a high yielding method of carbonyl group protection under mild,

Full text of DOI:10.1246/cl.2001.794

7
94
Chemistry Letters 2001
Highly Efficient Dithioacetalization of Carbonyl Compounds Catalyzed
with Iodine Supported on Neutral Alumina
#
##
Nabajyoti Deka and Jadab C. Sarma *
Organic Chemistry Division, Regional Research Laboratory, Jorhat 785006, Assam, India
(Received May 11, 2001; CL-010432)
Aldehydes and ketones are protected as their corresponding
reflux in dichloromethane. This may be due to homogeneity of
the reaction medium in solution phase. The carbonyl function
of a β-keto ester (methyl acetoacetate) could also be thioacetal-
ized by this method in a short period with a high yield. When
compared with the existing methods, the present method was
found to be superior in many respects. It is suitable to aldehy-
des and ketones both aliphatic and aromatic as well as α,β-
unsaturated carbonyl compounds, while the activity of lithium
dithioacetals with ethane-1,2-dithiol in the presence of a cat-
alytic amount of iodine supported on neutral alumina surface.
This is a high yielding method of carbonyl group protection
under mild, neutral and solvent free conditions.
Protection of carbonyl functions as their dithioacetals is an
important transformation in organic synthesis frequently used
during the course of a multi-step synthesis of complex mole-
cules.1 Moreover dithioacetal is an important intermediate
through which a carbonyl compound can be converted into its
8a
8b
triflate and lithium bromide is limited to aromatic and α,β-
unsaturated systems only. Moreover, in case of ketones the
reaction is very slow with these reagents. Both these reagents
are hygroscopic in nature and lithium triflate needs elevated
temperature for completion of the reaction. Although copper
2
parent hydrocarbon by reductive desulfurization method.
9
Normally dithioacetals are prepared by the acid catalyzed con-
densation of carbonyl compounds with thiols or dithiols.
triflate-silicagel reacts with both aliphatic and aromatic aldehy-
des and ketones yet the reaction is very slow (benzophenone, 24
h; camphor, 60 h) as compared to the present method (ben-
zophenone, 4 h; camphor, 4.5 h). This method is free from the
problem of Michael addition encountered in some cases of α,β-
3
WCl , TeCl and several other Lewis acid catalysts like BF -
6
4
3
etherate, ZnCl , AlCl , TiCl , LaCl , SiCl etc. have been
2
3
4
3
4
4
5
6
reported for this transformation. Sato et al. and Das et al.
1
3
had also reported two tin compounds as suitable catalysts.
Among many of the recently developed catalysts, solid catalysts
are gaining popularity due to easier handling, milder reaction
unsaturated systems with some reagents.
7
conditions and simpler work-up procedure.
8
9
Very recently Firouzabadi et al. and Anand et al. have
reported two different methods using solid catalysts under sol-
vent free conditions for thioacetalization reaction. Because of
1
0
our interest in iodine-catalyzed reactions, we ventured to
observe that iodine supported on neutral alumina under solvent
free conditions as well as in solution acted as a highly efficient
catalyst in the preparation of dithioacetals from carbonyl com-
pounds giving a fast and clean reaction with high yield. When
a carbonyl compound was treated with ethane-1,2-dithiol in the
presence of a catalytic amount (10%) of iodine supported on
neutral alumina surface, the corresponding dithioacetal was
1
1,12
obtained in 89 to 95% yield.
In a blank reaction, neutral
alumina alone without iodine was found to give no product.
The neutral alumina was the preferred choice as support to keep
the reaction medium under mild and neutral condition. Because
of the inherent acidity or basicity, other two forms of alumina
were not used. The results are presented in Table 1.
In the present method it was observed that dithioacetaliza-
tion of aldehydes proceeded more quickly than ketones. Yields
of the corresponding thioacetals of aldehydes were also found
to be a little higher than that of ketones. Hindered and unreac-
tive ketones such as benzophenone gave better yield only under
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
795
We thank Dr. N. C. Barua for constant encouragements,
the Director Dr. J. S. Sandhu FNA for providing the facilities
and N. D. thanks CSIR for an SRFship.
11 Procedure for preparation of the catalyst: The catalyst was
prepared by making a slurry of activated neutral alumina (1
g, Aldrich, standard grade, 150 mesh) with a solution of 51
mg (0.20 mmol) of iodine in 2 mL of dichloromethane.
The slurry was stirred magnetically at room temperature
for 30 minutes and the excess solvent was removed by
evaporation under reduced pressure and at low tempera-
ture. When the slurry became dry and free falling it was
ready for use.
12 Typical procedure for dithioacetalization: To a freshly pre-
pared catalyst (1 g, 0.2 mmol of iodine) under stirring, a
mixture of benzaldehyde (2 mmol) and ethane-1,2-dithiol
(2.2 mmol) was added and stirring continued for 10 min or
till the reaction was complete. For TLC monitoring, a
small amount of the solid reaction mixture was taken out
with a spatula and washed with a little amount of ethyl
acetate to get a solution. On completion the reaction mix-
ture was loaded on a short column of silica gel (60 to 120
mesh) and eluted with ethyl acetate. The organic layer was
washed with a dilute solution of sodium thiosulfate fol-
lowed by water and dried over anhydrous sodium sulfate.
Evaporation of the solvent under reduced pressure and
purification of the residue by coloumn chromatography
yielded the pure product.
References and Notes
#
Present address: Department de Phamacochimie
Moleculaire, Universite Joseph Fourier, UMR CNRS 5063,
France.
#
# Present address: JSPS Fellow, Department of
Environmental Chemistry & Materials, Okayama
University, 1-1 Naka 2-Chome, Tsushima, Okayama 700-
8
530, Japan.
1
2
a) P. J. Kocienski, “Protecting Groups,” Thieme, New
York (1994). b) T. W. Greene and P. G. M. Wuts,
“
Protective Groups in Organic Synthesis,” John Wiley &
Sons, New York (1999).
R. K. Olsen and J. O. Currier, Jr, in “ The Chemistry of the
Thiol Group,” ed. by S. Patai, John Wiley & Sons, New
York (1974), Part 2, p 519.
3
4
H. Firouzabadi, N. Iranpoor, and B. Karimi, Synlett, 1998,
7
39.
H. Tani, K. Masumoto, T. Inamasu, and H. Suzuki,
Tetrahedron Lett., 32, 2039 (1991) and references cited
therein.
5
a) T. Sato, E. Yoshida, T. Kobayashi, J. Otera, and H.
Nozaki, Tetrahedron Lett., 29, 3971 (1988). b) T. Sato, J.
Otera, and H. Nozaki, J. Org. Chem., 58, 4971 (1993).
N. B. Das, A. Nayak, and R. P. Sharma, J. Chem. Res. (S),
13 E. J. Corey and K. Shimoji, Tetrahedron Lett., 24, 169
(1983).
14 H. K. Patney, Tetrahedron Lett., 32, 2259 (1991).
15 Y. Kamitori, M. Hajo, R. Masuda, T. Kimura, and T.
Yashida, J. Org. Chem., 51, 1427 (1986).
6
7
1
993, 242.
a) H. K. Patney and S. Margan, Tetrahedron Lett., 37, 4621
1996). b) S. Chandrasekhar, M. Takhi, R. Y. Reddy, S.
Mohapatra, C. R. Rao, and K. V. Reddy, Tetrahedron, 53,
4997 (1997).
16 P. K. Chowdhury, J. Chem. Res. (S), 1993, 124.
1
(
17 a) H NMR (CDCl , 60 MHz) δ 4.15 (t, J = 6Hz, 1H), 2.95
3
(s, 4H), 1.75 to 1.05 (m, 28H), 0.75 (t, J = 6.5 Hz, 3H); IR
–
1
1
2950, 2900, 1480, 1220 cm . Anal. Calcd for C H S : C,
18 36 2
8
a) H. Firouzabadi, B. Karimi, and S. Eslami, Tetrahedron
Lett., 40, 4055 (1999). b) H. Firouzabadi, N. Iranpoor, and
B. Karimi, Synthesis, 1999, 58.
68.28; H, 11.46; S, 20.25%. Found: C, 68.27; H, 11.73; S,
1
20.08%. b) H NMR (CDCl , 60 MHz) δ 5.65 to 5.05 (m,
3
3H), 3.25 (s, 4H), 2.15 to 1.05 (overlapping multiplet,
11H), 0.90 (s, 3H), 0.80 (s, 3H); IR 2975, 2900, 1480,
9
1
R. V. Anand, P. Sarvanan, and V. K. Singh, Synlett, 1999,
–
1
4
15.
1380, 1250, 1050, 980 cm .Anal. Calcd for C H S : C,
15 24 2
0 a) N. Deka, D. J. Kalita, R. Borah, and J. C. Sarma, J. Org.
Chem., 62, 1563 (1997). b) R. Borah, N. Deka, and J. C.
Sarma, J. Chem. Res. (S), 1997, 110. c) D. J. Kalita, R.
Borah, and J. C. Sarma, Tetrahedron Lett., 39, 4573
67.11; H, 9.01; S, 23.89%. Found: C, 67.57; H, 9.08; S,
1
23.24%. c) H NMR (CDCl , 60 MHz) δ 7.40 (d, J = 8Hz,
3
1H), 6.45 to 6.05 (m, 2H), 3.53 (s, 3H), 3.20 (s, 4H), 2.55
(overlapping triplet, 4H), 2.45 to 2.00 (m, 2H); IR 2950,
2900, 1610, 1590, 1500, 1450, 1320, 1300, 1250, 1050
(1998). d) N. Deka and J. C. Sarma, Synth. Commun., 30,
–
1
4435 (2000). e) N. Deka and J. C. Sarma, J. Org. Chem.,
cm .Anal. Calcd for C H OS : C, 61.86; H, 6.39; O,
13 16 2
6
6, 1947 (2001).
6.34; S, 25.41%. Found: C, 61.32; H, 6.44; S, 25.86%.