1
398
N. C. Ganguly, S. K. Barik
PAPER
Table 2 reveals that a aryl dithioacetal that is deactivated 1,3-Propanedithiol, 1,2-ethanedithiol and benzenedithiol were pur-
chased from Sigma-Aldrich Chemie GmbH, Germany. Iodine and
due to the presence of a nitro group (entry 7) underwent
SDS were obtained from Merck, Germany and SRL, India, respec-
much slower deprotection than those activated with elec-
tron-releasing groups (entries 3–6, 9). The huge rate dif-
ferential may be exploited for preferential removal of
activated dithianes in the presence of nonactivated ana-
logues. This is demonstrated by facile selective deprotec-
tively. IR spectra were recorded on a Perkin-Elmer 2400-Series II
1
spectrometer. H NMR spectra were measured on a Bruker AM-
3
00L (300 MHz) spectrometer. Light petrol used refers to the frac-
tion boiling at 60–80 °C.
tion of 2-(4-hydroxyphenyl)-1,3-dithiane (entry 3) (90% Deprotection of 1,3-Dithianes and 1,3-Dithiolanes; 3,4-Methyl-
enedioxybenzaldehyde (Piperonal); Typical Procedure
yield) in an equimolar mixture with 2-(2-nitrophenyl)-
Finely pulverized I (12.8 mg, 0.05 mmol), 2-(3,4-methylenedi-
2
1
,3-dithiane (entry 7) upon treatment with 30% H O2
2
oxyphenyl)-1,3-dithiane (1; 242 mg, ~1 mmol) and finally 30%
(
0.45 mL) and I (5 mol%) in aqueous SDS for 25 minutes
2
H O (0.45 mL, 4 mmol) were added to an aqueous solution of SDS
2
2
and recovery of the latter in almost quantitative yield. 1,3-
(
5 mL, 57.8 mg, 0.2 mmol) and the mixture was vigorously stirred
Dithiolanes are also found to be more reluctant towards at r.t. for 30 min when its TLC examination showed complete dis-
2
9
cleavage than 1,3-dithianes, which are compatible with appearance of the starting material. The reaction was quenched by
the addition of aq 5% Na S O (5 mL) and the resulting mixture was
their more positive oxidation potentials than the corre-
2
2
3
4
e
extracted with EtOAc (3 × 3 mL). The combined organic extracts
sponding dithianes. An intermolecular competition ex-
periment performed with a mixture of 1 mmol each of 2-
were washed with H O (2 × 2 mL) and dried (Na SO ). It was con-
2
2
4
centrated and filtered through a short pad of silica gel (60–120
mesh, Spectrochem, India) using EtOAc–light petrol (1:19) as elu-
ent to give 3,4-methylenedioxybenzaldehyde (piperonal) (144 mg,
(
2-hydroxyphenyl)-1,3-dithiane (entry 4) and its 1,3-
dithiolane counterpart (entry 27) under optimal conditions
2
8
for 35 minutes resulted in 90:10 selectivity in favor of the 95%); mp 37–38 °C (EtOAc–light petrol) (Lit. mp 37 °C).
former. Even nonactivated dithianes (entries 12–15) were
Isolation of Butanal as 2,4-Dinitrophenylhydrazone Derivative
After Deprotection from its 1,3-Dithiane Derivative; Typical
cleaved within reasonable times. To investigate the cata-
lytic role of metal ions, particularly iron species, present
Procedure
in water that can possibly decrease the difference in cleav-
To an aqueous solution of SDS (10 mL, 115 mg, 0.4 mmol) were
age rate between activated and nonactivated dithianes, as
added powdered I (26 mg, 0.1 mmol), 2-butyl-1,3-dithiane (326
2
9
a
observed in IBX-mediated cleavage, we carried out sep-
mg, 2 mmol) (Table 2, entry 14) and 30% H O (0.9 mL, 8 mmol)
2
2
arate experiments of cleavage of 1,3-dithiane of cyclohex- and the mixture was stirred thoroughly at r.t. for 1.5 h. The mixture
anone (entry 12) using tap water that contained fair was then treated with aq 5% Na (6 mL), extracted with Et
2 × 3 mL) and dried. To the concentrated ethereal extract were add-
S
O
O
2
2
2
3
(
amounts of iron salts and deionized distilled water under
otherwise identical reaction conditions. Cleavage rate as
well as yield of cyclohexanone remained unaffected sug-
gesting the absence of metal ion catalysis. The reported
failure of cleavage of dithioacetals with one equivalent of
ed 2–3 drops of MeOH and then a methanolic solution of 2,4-dini-
trophenylhydrazine (0.6 g of the reagent in 5 mL of MeOH
containing 0.5 mL of concd H SO ) and kept for 0.5 h. The precip-
itated bright yellow crystals were collected by filtration and crystal-
lized from EtOAc–light petrol to give the corresponding 2,4-
2
4
3
0
28
FeCl3 supported our observation. However, lack of suf- dinitrophenylhydrazone (456 mg); mp 119–121 °C (Lit. mp
ficient cleavage rate difference of noncyclic thioacetals 123 °C), which corresponds to 130 mg of butanal (90% yield).
(
entries 30–32) and 1,3-dithianes precluded their discrim-
ination. Gratifyingly, acid-labile cinnamaldehyde (entry
6), furan-2-aldehyde (entry 17) were smoothly released
Acknowledgment
1
SKB thanks University of Kalyani for financial assistance by way
of a research fellowship. Facilities provided by DST-FIST Grant,
Government of India are also acknowledged.
from respective dithianes without overoxidation. The hy-
drolysis-prone aryl acetate (entry10), benzoate (entry 24),
and a number of phenol-protecting benzyl, TBDPS, TB-
DMS ethers and amino-protecting BOC and Cbz carbam-
ates were tolerated under the cleavage conditions further References
attesting to its mildness. Deprotections were carried out in
a 1–5 mmol range without loss of efficiency in terms of
yield and facility.
(
1) (a) Green, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis; Wiley: New York, 1999, 3rd ed..
b) Kocieneski, P. J. Protecting Groups; Thieme: Stuttgart,
994.
2) Gröbel, B.-T.; Seebach, D. Synthesis 1977, 357.
3) (a) Corey, E. J.; Ericson, B. W. J. Org. Chem. 1971, 36,
(
1
In conclusion, we have developed a facile deprotection
method of thioacetals and thioketals using 30% aqueous
H O and 5 mol% iodine catalyst in aqueous micellar en-
(
(
2
2
3553. (b) Corey, E. J.; Bock, M. G. Tetrahedron Lett. 1975,
vironment. Absence of overoxidation products for oxida-
tion-prone substrates, compatibility with a large number
of common functional and acid-sensitive protecting
groups, manipulative simplicity, and generality combined
with green features will hopefully make it a method of
choice for deprotection of thioacetals and thioketals.
2
643.
(4) (a) Nishide, K.; Yokota, K.; Nakamura, D.; Sumiya, T.;
Node, M.; Ueda, M.; Fuji, K. Tetrahedron Lett. 1993, 34,
3425. (b) Jones, P. S.; Ley, S. V.; Simkins, N. S.; Whittle,
A. J. Tetrahedron 1986, 42, 6519. (c) Smith, R. A.; Hannah,
D. J. Synth. Commun. 1979, 9, 301. (d) Ho, T.-L.; Wong,
C. M. Can. J. Chem. 1972, 50, 3740. (e) Oksdath-Mansilla,
G.; Peñéñory, A. B. Tetrahedron Lett. 2007, 48, 6150.
(
f) Haroutounian, S. A. Synthesis 1995, 39. (g) Barton,
D. H. R.; Cussons, N. J.; Ley, S. V. J. Chem. Soc., Chem.
Commun. 1977, 751.
Synthesis 2009, No. 8, 1393–1399 © Thieme Stuttgart · New York