Novel oxidative α-tosyloxylation of alcohols with iodosylbenzene and p-toluenesulfonic acid and its synthetic use for direct preparation of heteroaromatics

Article abstract of DOI:10.1021/jo030045t

α-Tosyloxyketones and α-tosyloxyaldehydes were directly prepared from alcohols by treatment with iodosyl-benzene and p-toluenesulfonic acid monohydrate in good yields. This method can be used for the direct preparation of thiazoles, imidazoles, and imidaz

Full text of DOI:10.1021/jo030045t

TABLE 1. Oxid a tive r-Tosyloxyla tion of
-P h en yleth a n ol Usin g Va r iou s Hyp er va len t Iod in e
Rea gen ts
Novel Oxid a tive r-Tosyloxyla tion of
Alcoh ols w ith Iod osylben zen e a n d
p-Tolu en esu lfon ic Acid a n d Its Syn th etic
Use for Dir ect P r ep a r a tion of
Heter oa r om a tics
1
†
†
,†,‡
Makoto Ueno, Takahiro Nabana, and Hideo Togo*
Graduate School of Science and Technology, and
Department of Chemistry, Faculty of Science, Chiba
University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522 J apan
togo@scichem.s.chiba-u.ac.jp
Received February 3, 2003
Abstr a ct: R-Tosyloxyketones and R-tosyloxyaldehydes were
directly prepared from alcohols by treatment with iodosyl-
benzene and p-toluenesulfonic acid monohydrate in good
yields. This method can be used for the direct preparation
of thiazoles, imidazoles, and imidazo[1,2-a]pyridines from
alcohols in good to moderate yields by the successive
treatment with iodosylbenzene and p-toluenesulfonic acid
monohydrate, followed by thioamides, benzamidine, and
paper, we would like to report a novel direct oxidative
R-tosyloxylation of alcohols. This method was successfully
applied to the direct preparation of thiazoles, imidazoles,
and imidazo[1,2-a]pyridines by the treatment of alcohols
with iodosylbenzene and p-toluenesulfonic acid and
subsequent treatment with thioamides, benzamidine, and
2
-aminopyridine, respectively.
2
-aminopyridine, respectively. The key step in this reac-
Today, extensive studies on hypervalent iodine com-
tion is the formation of aldehydes and ketones. To our
knowledge, the direct preparation of R-tosyloxyketones
from alcohols with iodosylbenzene and p-toluenesulfonic
acid monohydrate has not hitherto been reported. At first,
the reactivity of hypervalent iodine reagents, i.e., iodosyl-
benzene, 4-methyl-1-iodosylbenzene, 3-(trifluoromethyl)-
1-iodosylbenzene, (diacetoxyiodo)benzene, 4-methyl-1-(di-
acetoxyiodo)benzene, and 3-(trifluoromethyl)-1-(diacetoxy-
iodo)benzene, in the oxidative R-tosyloxylation of 1-phen-
ylethanol in the presence of p-toluenesulfonic acid mono-
hydrate in acetonitrile was studied as shown in Table 1.
Here, iodosylarenes showed better reactivity than (di-
acetoxyiodo)arenes. In the substituent effect of iodosy-
larenes, the parent iodosylbenzene showed the most
effective reactivity. Thus, on the basis of these results,
the oxidative R-tosyloxylation of alcohols with iodosyl-
benzene and p-toluenesulfonic acid monohydrate in ac-
etonitrile was carried out as shown in Table 2. Generally,
secondary alcohols give R-tosyloxyketones in high yields,
whereas primary alcohols give R-tosyloxyaldehydes in
moderate yields. The reactive species for the oxidative
R-tosyloxylation of alcohols should be [hydroxy(tosyloxy)-
iodo]benzene (HTIB). Practically, the same treatment of
alcohols with HTIB generates the corresponding R-tosyl-
pounds have been carried out, and the synthetic use of
these compounds has been well studied. Among them,
1
[
hydroxy(tosyloxy)iodo]benzene (Koser’s reagent, HTIB)
2
is a useful reagent for R-tosyloxylation of ketones.
R-Tosyloxyketones are very important precursors for the
construction of various heterocyclic compounds such as
3
thiazoles, selenazoles, oxazoles, imidazoles, etc. In this
†
Graduate School of Science and Technology.
Department of Chemistry.
‡
(1) Varvoglis A. Hypervalent Iodine in Organic Synthesis; Academic
Press: San Diego, 1997. Recent reviews: (a) Ochiai, M. Rev. Heteroat.
Chem. 1989, 2, 92. (b) Moriarty, R. M.; Vaid, R. K. Synthesis 1990,
4
31. (c) Stang, P. J .; Angew. Chem., Int. Ed. Engl. 1992, 31, 274. (d)
Prakash, O.; Saini, N.; Sharma, P. K. Synlett 1994, 221. (e) Kitamura,
T. Yuki Gosei Kagaku Kyokaishi 1995, 53, 893. (f) Stang, P. J .;
Zhdankin, V. V. Chem. Rev. 1996, 96, 1123. (g) Umemoto, T. Chem.
Rev. 1996, 96, 1757. (h) Kita, Y.; Takada, T.; Tohma, H. Pure Appl.
Chem. 1996, 68, 627. (i) Togo, H.; Hoshina, Y.; Nogami, G.; Yokoyama,
M. Yuki Gosei Kagaku Kyokaishi 1997, 55, 90. (j) Varvoglis, A.
Tetrahedron 1997, 53, 1179. (k) Zhdankin, V. V. Rev. Heteroat. Chem.
1
997, 17, 133. (l) Muraki, T.; Togo, H.; Yokoyama, M. Rev. Heteroat.
Chem. 1997, 17, 213. (m) Kitamura, T.; Fujiwara, Y. Org. Prep. Proced.
Int. 1997, 29, 409. (n) Varvoglis, A.; Spyroudis, S. Synlett 1998, 221.
(o) Zhdankin, V. V.; Stang, P. J . Tetrahedron 1998, 54, 1998. (p)
Moriarty, R. M.; Prakash, O. Adv. Heterocycl. Chem. 1998, 69, 1. (q)
Togo, H.; Katohgi, M. Synlett 2001, 565. (r) Zhdankin, V. V.; Stang, P.
J . Chem. Rev. 2002, 102, 2523.
(
2) (a) Koser, G. F.; Wettach, R. H. J . Org. Chem. 1976, 41, 3609.
(
b) Koser, G. F.; Wettach, R. H. J . Org. Chem. 1977, 42, 176. (c) Koser,
G. F.; Wettach, R. H.; Smith, C. S. J . Org. Chem. 1980, 45, 1542. (d)
Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.; Wettach, R. H.
J . Org. Chem. 1982, 47, 2487. (e) Moriarty, R. M.; Penmasta, R.;
Awasthi, A. K.; Epa, W. R.; Prakash, I. J . Org. Chem. 1989, 54, 1101.
(3) (a) Koser, G. F.; Wettach, R. H. J . Org. Chem. 1977, 42, 1476.
(b) Moriarty, R. M.; Vaid, R. K.; Hopkins, T. E.; Vaid, B. K.; Prakash,
O. Tetrahedron Lett. 1990, 31, 201. (c) Moriarty, R. M.; Vaid, B. K.;
Duncan, M. P.; Levy, S. G.; Prakash, O.; Goyal, S. Synthesis 1992,
845. (d) Prakash, O.; Goyal, S. Synthesis 1992, 629. (e) Prakash, O.;
Rani, N.; Goyal, S. J . Chem. Soc. Perkin Trans. 1 1992, 707. (f)
Prakash, O.; Saini, N.; Sharma, P. K. Synlett 1994, 221. (g) Prakash,
O.; Saini, N.; Sharma, P. K. Heterocycles 1994, 38, 409.
(
f) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett 1990, 365. (g)
Tuncay, A.; Dustman, J . A.; Fisher, G.; Tuncay, C. I. Tetrahedron Lett.
992, 33, 7647. (h) Vrama, R. S.; Kumar, D.; Liesen, P. J . J . Chem.
Soc., Perkin Trans. 1 1998, 4093. (i) Lee, J . C.; Choi, J u-H. Synlett
1
2
001, 234. (j) Nabana, T,; Togo, H. J . Org. Chem. 2002, 67, 4362.
1
0.1021/jo030045t CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/11/2003
6
424
J . Org. Chem. 2003, 68, 6424-6426

TABLE 2. Oxid a tive r-Tosyloxyla tion of Alcoh ols
SCHEME 2. Oxid a tive r-P h osp h or yloxyla tion of
Alcoh ols
R
R′
yield (%)
96
C6H5
H
H
H
H
a
p-CH3C6H4
p-ClC6H4
p-O2NC6H4
C6H5
C6H5
n-C5H11
H
84
96
99
94
87
80
a
CH3
TABLE 3. Dir ect P r ep a r a tion of Heter ocyclic
Com p ou n d s
a
n-C7H15
n-C4H9
n-C11H23
(CH2)3C6H5
a,b
a
53
H
49
52
a,b
-
(CH2)4-
a
Reaction time was 2.5 h. b Reaction temperature was 60 °C.
SCHEME 1. Oxid a tive r-Tosyloxyla tion of Alcoh ols
w ith HTIB
R1
C6H5
p-ClC6H4
p-NO2C6H4
C6H5
C6H5
p-ClC6H4
C6H5
R2
R3
X
yield (%)
A
A
A
A
A
A
B
B
H
H
H
H
H
H
H
H
CH3
CH3
CH3
C6H5
C6H5
C6H5
S
S
S
S
NH
NH
59
53
64
48
48
64
83
48
oxyketones in good yields as shown in Scheme 1. How-
ever, the yields of the products strongly depend on the
alcohols used. Especially, treatment of alcohols bearing
an electron-rich aromatic group, such as a tolyl group or
an anisyl group, with HTIB gives the corresponding
R-tosyloxyketones in poor yields, and R-tosyloxyaldehydes
from primary alcohols with HTIB were not formed at all.
Thus, the present method for the direct R-tosyloxylation
of alcohols with iodosylbenzene and p-toluenesulfonic acid
monohydrate is highly effective and useful for the
preparation of R-tosyloxyketones and R-tosyloxyalde-
hydes.
p-ClC6H4
On the basis of these results, direct preparation of
thiaozles, as typical heteroaromatics, was carried out by
the treatment of alcohols with iodosylbenzene and p-
toluenesulfonic acid monohydrate and subsequent treat-
ment with thioamide in the presence of potassium
carbonate. As shown in Table 3, thiazoles were obtained
in good yields from the starting alcohols. Imidazoles and
imidazo[1,2-a]pyridines were also obtained in good to
moderate yields by the same treatment of alcohols with
iodosylbenzene and p-toluenesulfonic acid monohydrate,
followed by the reaction with benzamidine and 2-ami-
nopyridine in the presence of potassium carbonate,
respectively.
The effect of sulfonic acids with methanesulfonic acid,
p-toluenesulfonic acid, and p-nitrobenzenesulfonic acid
was studied, and consequently p-toluenesulfonic acid
showed the most effective reactivity. Moreover, as a part
of our study on environmentally benign organic synthe-
4
sis we have studied the preparation of R-tosyloxy-
acetophenone from 1-phenylethanol in a room-tempera-
ture ionic liquid (1-butyl-3-methylimidazolium hexafluo-
rophosphate) media and a solvent-free reaction. However,
the yields were decreased to 30% and 53%, respectively.
Thus, effective acceleration for the reactions of the ionic
liquid media and solvent-free conditions was not ob-
served.
On the basis of these results, a reasonable reaction
mechanism is shown in Scheme 3. Here, [hydroxy-
(tosyloxy)iodo]benzene 1 is smoothly formed in situ by
the reaction of iodosylbenzene and p-toluenesulfonic acid
2
monohydrate. Alcohols reacts with compound 1 to form
Under the same conditions, treatment of 1-phenyl-
ethanol and 1-phenylpropanol with iodosylbenzene and
diphenylphosphoric acid generates R-(diphenylphos-
phoryloxy)acetophenone and R-(diphenylphosphoryloxy)-
propiophenone in 79% and 62% yields, respectively, as
shown in Scheme 2.
the corresponding carbonyl compounds 3 via the inter-
mediates 2. In the presence of p-toluenesulfonic acid,
carbonyl compounds 3 tautomerize to the corresponding
enol forms 3′, which then react with compound 1 to
provide R-tosyloxyketones or R-tosyloxyaldehydes via the
intermediates 4 and 4′. Practically, under the same
conditions, treatment of alcohols with compound 1 gener-
ates the corresponding R-tosyloxycarbonyl compounds as
mentioned in Scheme 1, and the same treatment of
carbonyl compounds with iodosylbenzene and p-toluene-
(4) (a) Togo, H.; Nogami, G.; Yokoyama, M. Synlett 1998, 534. (b)
Abe, S.; Sakuratani, K.; Togo, H. J . Org. Chem. 2001, 66, 6174. (c)
TEMPO-mediated oxidation of alcohols with poly[4-(diacetoxyiodo)-
styrene]: Sakuratani, K.; Togo, H. Synthesis 2003, 21.
J . Org. Chem, Vol. 68, No. 16, 2003 6425

SCHEME 3. Rea ction Mech a n ism for Oxid a tive
Exp er im en ta l Section
r-Tosyloxyla tion of Alcoh ols
Gen er a l. All reactions were carried out under an argon
atmosphere. 1H NMR spectra were recorded on a 400 MHz
spectrometer. Chemical shifts are reported as ppm downfield
from tetramethylsilane (TMS) in δ units, and J values are given
in Hz. IR spectra were recorded on a FT/IR-200 spectrometer.
Microanalyses were performed with 240B and 240 elemental
analyzers at Chemical Analysis Center of Chiba University.
Melting points were determined on a melting point apparatus
in open capillary tubes and are uncorrected. Silica gel 60 was
used for column chromatography, Kieselgel 60 F254 was used
for TLC, and Wakogel B-5F was used for preparative TLC.
Gen er a l P r oced u r e for Oxid a tive R-Tosyloxyla tion of
Alcoh ols. To a solution of alcohol (1.0 mmol) in acetonitrile (10
mL) were added p-toluenesulfonic acid monohydrate (2.5 mmol)
and iodosylbenzene (3.0 mmol). The mixture was refluxed for
1
.5 h under an argon atmosphere, and then the reaction mixture
was poured into water and extracted with chloroform three
times. The combined organic layer was dried over Na SO . After
2
4
filtration, the solvent was evaporated under reduced pressure,
and the residue was purified by preparative TLC on silica gel
(
eluent, hexane/ethyl acetate ) 3/1) to give the corresponding
R-tosyloxyketone.
Gen er a l P r oced u r e for Dir ect P r ep a r a tion of Th ia zoles
fr om Alcoh ols. To a solution of alcohols (1.0 mmol) in aceto-
nitrile (10 mL) were added p-toluenesulfonic acid monohydrate
(2.5 mmol) and iodosylbenzene (3.0 mmol). The mixture was
refluxed for 1.5 h under an argon atmosphere, and then the
reaction mixture was poured into water and extracted with
chloroform three times. The combined organic layer was dried
SCHEME 4. Oxid a tive r-Tosyloxyla tion of Keton es
2 4
over Na SO . After filtration, the solvent was removed under
reduced pressure. Acetonitrile (6 mL), potassium carbonate (1.5
mmol), and thioamide (1.2 mmol) were added to the residue. The
mixture was refluxed for 5 h under an argon atmosphere, and
then the reaction mixture was poured into water and extracted
with chloroform three times. The combined organic layer was
2 4
dried over Na SO . After filtration, the solvent was evaporated
under reduced pressure and the residue was purified by pre-
parative TLC on silica gel (eluent, hexane/ethyl acetate ) 3/1)
to give the corresponding thiazole.
sulfonic acid monohydrate produces the corresponding
R-tosyloxycarbonyl compounds as shown in Scheme 4.
In conclusion, the present reaction is a simple and
facile method for the direct preparation of R-tosyloxy-
aldehydes and R-tosyloxyketones from alcohols with
iodosylbenzene and p-toluenesulfonic acid monohydrate
and can be used for the direct preparation of hetero-
aromatics such as thiazoles, imidazoles, and imidazo[1,2-
a]pyridine, respectively, from secondary and primary
alcohols, by the successive treatment with iodosylbenzene
and p-toluenesulfonic acid monohydrate, followed by the
treatment with thioamide, amidine, and 2-aminopyridine
in the presence of potassium carbonate.
Ack n ow led gm en t. Financial support from a Grant-
in-Aid for Scientific Research (13554028) from the
Ministry of Education, Science, Sports and Culture is
gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for all R-tosyloxyketones, R-tosyloxyaldehydes, thiazoles,
1
imidazoles, and imidazo[1,2-a]pyridines and copies of their H
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O030045T
6
426 J . Org. Chem., Vol. 68, No. 16, 2003