Convenient and eco-friendly method for the conversion of benzylic alcohols into aldehydes, ketones, and carboxylic acids using NaOCl without any additives in 1,2-dimethoxyethane

Article abstract of DOI:10.1055/s-0033-1338856

Oxidation of benzylic alcohols to aldehydes, ketones, and carboxylic acids using NaOCl in 1,2-dimethoxyethane without any additives has been developed. 4-Methylbenzyl alcohol and diphenyl methanol were converted into the corresponding aldehyde and ketone in 97% and 92% yield, respectively. Furthermore, 4-nitrobenzyl alcohol was directly converted into the corresponding carboxylic acid in 99% yield. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0033-1338856

1438▌
LETTER
lCettoernvenient and Eco-Friendly Method for the Conversion of Benzylic Alcohols
into Aldehydes, Ketones, and Carboxylic Acids Using NaOCl without any
Additives in 1,2-Dimethoxyethane
Oxidation of Various Kinds of Benzylic Alcohols
Naohiro Fukuda, Takeshi Kajiwara, Tomoaki Katou, Keisuke Majima, Tomomi Ikemoto*
Chemical Development Laboratories, CMC Center, Takeda Pharmaceutical Company Limited, 2-17-85, Jusohonmachi, Yodogawa-ku, Osaka,
5
32-8686, Japan
Fax +81(6)63006251; E-mail: tomomi.ikemoto@takeda.com
Received: 28.03.2013; Accepted after revision: 25.04.2013
tions with NaOCl are well known to be versatile for oxi-
dizing various primary and secondary alcohols to the
corresponding aldehydes and ketones under mild condi-
Abstract: Oxidation of benzylic alcohols to aldehydes, ketones,
and carboxylic acids using NaOCl in 1,2-dimethoxyethane without
any additives has been developed. 4-Methylbenzyl alcohol and di-
phenyl methanol were converted into the corresponding aldehyde
1
4
tions. Aqueous NaOCl used for TEMPO oxidation is a
and ketone in 97% and 92% yield, respectively. Furthermore, 4- safe and inexpensive reagent, and there are many reports
1
4,16–18
nitrobenzyl alcohol was directly converted into the corresponding regarding the oxidation of alcohol using NaOCl.
carboxylic acid in 99% yield.
Generally, the ability of NaOCl itself for the oxidation of
Key words: NaOCl, 1,2-dimethoxyethane, oxidation, alcohol, car- alcohols is not strong because of the low solubility of hy-
–
19
bonyl compound
pochlorite ions (OCl ) in organic solvent. Therefore it is
essential to add some additives for higher conversion. One
method is the use of alumina to give a supported hypo-
The selective oxidation of alcohols to the corresponding chlorite reagent, which offers selective and convenient
1
8
carbonyl compounds is one of the most significant and oxidation of benzyl and secondary alcohols, and phase-
widely used methods in organic synthesis. Therefore, a transfer catalysts have been used as additives in two-phase
16
number of methods have been developed. Among them, systems. Oxidation in acetic acid has also been used, but
1
7
stoichiometric amounts of metal or organic oxidants, such it easily generates toxic chlorine gas.
1
2
4
as chromium(VI)-based oxidants, manganese dioxide,
However, the oxidation reactions reported above involve
drawbacks in terms of safety, toxicity, handling, and the
removal of heavy metals. Hence there is still a strong de-
mand for more convenient and greener methods for the
oxidation of alcohols. Herein, we report the oxidation of
alcohols to the corresponding carbonyl compounds using
NaOCl without any additives.
3
activated dimethylsulfoxides, and hypervalent iodines
have been used for this transformation. Although these
methods are useful for alcohol oxidation, some issues re-
main to be addressed. Stoichiometric oxidations using
heavy metals usually produce toxic metal-containing
waste. Swern oxidation using dimethylsulfoxide and oxa-
lyl chloride must be conducted at cryogenic temperature
due to the instability of the reaction intermediate, chloro-
At the outset of our study, the effect of different solvents
containing 10% (w/w) aqueous NaOCl was investigated,
taking oxidation of biphenyl-4-methyl alcohol (1a) as a
model substrate (Table 1). Alcohol 1a was treated in
methanol for four hours under the reported conditions to
5
dimethylsulfonium chloride. Hypervalent iodines such as
Dess–Martin periodinane and IBX are known for their ex-
plosive character.6
Meanwhile, metal-catalyzed systems for the highly effi-
cient oxidation of alcohols using co-oxidants such as ox-
20
give 2a in 14% yield (Table 1, entry 1). The yield in-
creased slightly to 32% and 40%, respectively, when ethyl
acetate and acetonitrile were used in place of methanol as
the solvent (Table 1, entries 2 and 3). Only trace amounts
of 2a were produced in acetone, toluene, tetrahydrofuran,
and diisopropyl ether (Table 1, entries 4–7), but to our de-
light, 93% of 2a was obtained in 1,2-dimethoxyethane
7
8
9
10
ygen, hydrogen peroxide, acetone, or NaOCl have
been developed due to the growing requirement for envi-
ronmentally benign reaction systems. Furthermore, dehy-
drogenative oxidations of alcohols catalyzed by
1
1
12
ruthenium and iridium have been reported by numer-
ous groups.13 Although these methods are practical in
terms of producing less metal-containing waste, trace
metal contamination of product, especially for pharma-
ceutical use, requires tedious treatment for removal of
metal residues. Therefore numerous nonmetal-catalyzed
(
DME) along with 2% of 3a (Table 1, entry 8). Since the
oxidation in DME showed the best result among the sol-
vents with ether groups, we then attempted the oxidation
in solvents with two or three ether groups to investigate
the effect of the coordination ability of the ether groups.
Reaction in 1,4-dioxane showed moderate enhancement
of oxidation to afford 2a in 66% yield (Table 1, entry 9).
Comparatively, bis(2-methoxyethyl)ether was inferior to
DME and 1,4-dioxane (Table 1, entry 10). While reaction
in DME gave a two-phase system, the reaction phases
1
4,15
oxidations of alcohols have been also developed.
,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) oxida-
2
SYNLETT 2013, 24, 1438–1442
Advanced online publication: 10.06.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1338856; Art ID: ST-2013-U0273-L
Georg Thieme Verlag Stuttgart · New York
©

LETTER
Oxidation of Various Kinds of Benzylic Alcohols
1439
Table 1 Oxidation of 1a with Aqueous NaOCl in Various Solvents
that two ether groups affected the reactivity of oxidation
using NaOCl irrespective of the phase system. Although
the detailed effect was not clear, it was postulated that
chelation of the sodium cation by DME and 1,4-dioxane
1
0% aq NaOCl
(
1.8 equiv)
4
-PhC6H4CH2OH
4-PhC6H4CHO 4-PhC6H4CO2H
2a 3a
solvent (20 v/w)
r.t., 4 h
1a
2
1
enhanced the reactivity.
Entry Solvent
Yield of 1a Yield of 2a Yield of 3a
(
Next, the scope on 10% NaOCl oxidation of 1 in DME
leading to the corresponding carbonyl compounds was in-
vestigated, as shown in Table 2. After 2.4 equivalents of
NaOCl were added to the solution of 1b in DME, the re-
action mixture was stirred for four hours to give the alde-
hyde 2b in 73% and the carboxylic acid 3b in 2% with 1b
%)a
(%)a
(%)a
1
2
3
4
5
6
7
8
9
0
MeOH
EtOAc
MeCN
acetone
toluene
THF
82
59
56
98
97
98
96
5
14
32
40
<1
<1
2
<1
5
2
22
in 24% yield (Table 2, entry 1). In the course of this re-
action, the reaction temperature increased sharply at about
<1
1
20 minutes after addition and quickly reached about 30
°C. This phenomenon gives a potential safety issue in con-
trolling the reaction, especially for large-scale prepara-
tion. Therefore, 2.3 equivalents of NaOCl were added
portionwise to the solution of 1b in DME while keeping
<1
<1
2
i-Pr O
3
2
2
2
the reaction temperature below 30 °C. The reaction of
b with portionwise addition proceeded smoothly to pro-
DME
93
66
41
1
1,4-dioxane
(MeOCH CH ) O
31
52
2
vide 2b in 97% yield (Table 2, entry 2). Similarly, while a
single addition of NaOCl at one time provided 2c in 48%
yield, the portionwise addition increased the conversion to
give 2c in 94% yield (Table 2, entries 3 and 4). Addition-
ally, the position of the functional-group substitution af-
fected the oxidation. The oxidation of (2-
1
1
2
2 2
a
The yields were determined by HPLC using authentic samples as ref-
erence.
were homogeneous in the cases of 1,4-dioxane and bis(2- methoxylphenyl)methanol (1d) decreased the conversion
methoxyethyl)ether. From these results, it was suggested compared to 1b to give 2d in 80% yield (Table 2, entry 5).
Table 2 Conversion of Various Alcohols with Aqueous NaOCl in DMEa
R1
R1
R1
O
OH
10% aq NaOCl
DME
O
R2
R2
OH
1
2
3
(
for R2 = H)
Entry
Substrate
4-MeC H CH OH (1b)
NaOCl (equiv) Conditions
Yield of 1 (%)c Yield of 2 (%)c Yield of 3 (%)c
1
2
3
4
5
6
7
8
9
2.4
2.3b
2.4
2.3b
2.8b
2.4
1.0
2.4
1.4
2.8
r.t., 4 h
r.t., 4 h
r.t., 4 h
r.t., 4 h
r.t., 4 h
r.t., 4 h
0 °C, 4 h
r.t., 4 h
r.t., 1.5 h
24
3
73
97
48
94
80
90
37
<1
90
<1
2
6
4
2
1b
4-MeOC H CH OH (1c)
<1
<1
<1
<1
2
44
4
6
4
2
1c
2-MeOC H CH OH (1d)
2
6
4
2
4-ClC H CH OH (1e)
8
6
4
2
4-O NC H CH OH (1f)
18
<1
2
43
2
6
4
2
1f
4-MeO CC H CH OH (1g)
99 (93d)
8
2
6
4
2
10
11
12
1g
r.t., overnight
<1
77
OH
1.8
2.8
r.t., 4 h
<1
<1
52
<1
43
99
N
1
h
1h
r.t., overnight
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1438–1442

1440
N. Fukuda et al.
LETTER
Table 2 Conversion of Various Alcohols with Aqueous NaOCl in DMEa (continued)
R1
R1
R1
O
OH
10% aq NaOCl
DME
O
R2
R2
OH
1
2
3
(
for R2 = H)
Entry
Substrate
NaOCl (equiv) Conditions
Yield of 1 (%)c Yield of 2 (%)c Yield of 3 (%)c
OH
OH
1
1
1
3
4
5
2.4
2.4
2.4
r.t., 4 h
r.t., 4 h
r.t., 4 h
68
46
16
31
<1
O
1
1
i
S
many products
many products
j
OH
OH
1
1
k
l
1
6
7
2.4
2.4
r.t., 4 h
r.t., 4 h
n.r.e
OH
1
7
92 (90d)
–
–
1
m
OH
1
8
9
2.4
2.4
r.t., 4 h
r.t., 4 h
<1
<1
98
F
F
1
n
OH
OH
1
99d
–
–
1
1
o
Me
2
0
1
2.4
2.4
r.t., 4 h
r.t., 4 h
n.r.e
<1
p
9
4
2
benzoin (1q)
<1
benzoic acid
a
b
c
d
e
NaOCl was added to the solution of substrate in DME at the same time.
NaOCl was slowly added to the solution of substrate in DME.
The yields were determined by HPLC analysis using authentic samples as reference.
Isolated yields.
Reaction did not proceed at all.
The substrates containing electron-withdrawing groups tron-withdrawing groups, 1f and 1g, showed competitive
on the benzene ring were more active than those with elec- reaction between the conversion of alcohol into aldehyde
tron-donating groups. The compound 1e reacted with 2.4 and from aldehyde into carboxylic acid, compared with
equivalents of NaOCl over four hours to give 2e in 90% the electron-donating groups, 1b and 1c (Table 2, entries
yield (Table 2, entry 6). The benzyl alcohols with elec- 7–10). The reaction of 1f gave aldehyde 2f in 37% yield
Synlett 2013, 24, 1438–1442
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidation of Various Kinds of Benzylic Alcohols
1441
and carboxylic acid 3f in 43% yield, even though only 1.0
equivalent of NaOCl was used at 0 °C. On the other hand,
the oxidation with 2.4 equivalents of NaOCl directly con-
verted 1f into 3f in 99% yield. The reaction products of
ester derivatives, 2g and 3g, could be controlled by the
amount of NaOCl. The reaction of 1g with 1.4 equivalents
of NaOCl at room temperature for 1.5 hours gave 2g in
Jones, E. R. H.; Lemin, A. J. J. Chem. Soc. 1953, 2548.
c) Collins, J. C.; Hess, W. W.; Frank, F. J. Tetrahedron Lett.
968, 9, 3363. (d) Corey, E. J.; Suggs, J. W. Tetrahedron
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Georgoulis, C.; Stevens, C. L.; Vijayakumaran, K.
Tetrahedron Lett. 1985, 26, 1699.
(
1
2
3
90% yield, while the use of 2.8 equivalents of NaOCl at
(2) Fatiadi, A. J. Synthesis 1976, 133.
3) (a) Pitzner, K. E.; Moffatt, J. G. J. Am. Chem. Soc. 1965, 87,
(
room temperature overnight converted 1g into 3g in 77%
yield. Traditionally, two steps are required to oxidize al-
cohols, first into aldehydes followed by further oxidation
to carboxylic acids. However, our reaction system was
found to provide an alternative method for the direct oxi-
dation of primary alcohols to carboxylic acids. Heterocy-
clic derivatives showed similar reactivity to 1a–g. While
the oxidation of 2-pyridinemethyl alcohol (1h) with 1.8
equivalents of NaOCl provided a mixture of 2h and 3h,
increasing the amount of NaOCl to 2.8 equivalents afford-
ed 3h in 99% yield (Table 2, entries 11 and 12). The oxi-
dation of 2-furylmethanol (1i) was found to proceed
slowly to give 2i in 31% yield, with 68% of 1i remaining
5
1
661. (b) Pitzner, K. E.; Moffatt, J. G. J. Am. Chem. Soc.
965, 87, 4214. (c) Albright, J. D.; Goldman, L. J. Am.
Chem. Soc. 1965, 87, 5671. (d) Parikh, J. R.; Doering, W. E.
J. Am. Chem. Soc. 1967, 89, 5505. (e) Omura, K.; Sharrma,
A. K.; Swern, D. J. Org. Chem. 1976, 41, 957. (f) Epstein,
W. W.; Sweat, F. W. Chem. Rev. 1967, 67, 247.
(
4) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(b) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277. (c) Meyer, S. D.; Schreiber, S. L. J. Org. Chem. 1994,
5
9, 7549. (d) Frigerio, M.; Santagostino, M. Tetrahedron
Lett. 1944, 35, 8019. (e) Corey, E. J.; Palani, A. Tetrahedron
Lett. 1995, 36, 3485. (f) Frigerio, M.; Santagostino, M.;
Sputore, S.; Palmisano, G. J. Org. Chem. 1995, 60, 7272.
(g) De Munari, S.; Frigerio, M.; Santagostino, M. J. Org.
Chem. 1996, 61, 9272.
(Table 2, entry 13). On the other hand, the reactions of 1j
(
5) (a) Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651.
and 1k gave multiple products, and the reaction of 3-phe-
nyl-1-propanol (1l) did not proceed at all (entries 14–16).
(b) Mancuso, A. J.; Swern, D. Chem. Rev. 1981, 81, 165.
(
6) Plumb, J. B.; Harper, D. J. Chem. Eng. News 1990, 3.
Finally, secondary alcohols were also examined. When
(7) (a) Blackburn, T. F.; Schwartz, J. J. Chem. Soc., Chem.
Commun. 1977, 157. (b) Nishimura, T.; Onoue, T.; Ohe, K.;
Uemura, S. Tetrahedron Lett. 1998, 39, 6011.
1m, 1n, and 1o were treated under the conditions shown,
the desired products were obtained in 92%, 98%, and 99%
2
4
(c) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. J. Org.
Chem. 1999, 64, 6750. (d) ten Brink, G.-J.; Arends, I. W. C.
E.; Sheldon, R. A. Adv. Synth. Catal. 2002, 344, 355.
yield, respectively (Table 2, entries 17–19). However,
the oxidation of 1p did not proceed (Table 2, entry 20).
Benzoin (1q) did not give the corresponding ketone, but
benzoic acid in 94% yield owing to cleavage of the car-
bon–carbon single bond facilitated by a strong electron-
withdrawing group (Table 2, entry 21).
(
e) Schultz, M. J.; Park, C. C.; Sigman, M. S. Chem.
Commun. 2002, 3034. (f) ten Brink, G.-J.; Arends, I. W. C.
E.; Hoogenraad, M.; Verspui, G.; Sheldon, R. A. Adv. Synth.
Catal. 2003, 345, 497. (g) Bailie, D. S.; Clendenning, G. M.
A.; Muldoon, M. J. Chem. Commun. 2010, 7238.
In conclusion, we have developed a convenient oxidation
of various kinds of benzylic alcohols using the safe and
readily available reagent NaOCl in DME as solvent, lead-
ing to carbonyl compounds. Benzyl alcohol analogues
were converted into the corresponding aldehydes or ke-
tones. The oxidation of substrates containing electron-
withdrawing groups directly afforded the corresponding
carboxylic acids in high yield. To the best of our knowl-
edge, this is the first reported example of the oxidation of
alcohols using NaOCl as the oxidant without any addi-
tives under mild conditions. Therefore, this reaction has
the notable feature that the only waste product after oxida-
tion is NaCl, which makes it a green and practical strategy
to afford carbonyl compounds.
(
h) Csjernyik, G.; Éll, A. H.; Fadini, L.; Pugin, B.; Bäckvall,
J.-E. J. Org. Chem. 2002, 67, 1657. (i) Jiang, B.; Feng, Y.;
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L.-Y.; Li, J.; Lv, Y.; Zhang, H.-Y.; Gao, S. J. Organomet.
Chem. 2011, 696, 3257.
(
8) (a) Barak, G.; Dakka, J.; Sasson, Y. J. Org. Chem. 1988, 53,
3
553. (b) Sato, K.; Aoki, M.; Takagi, J.; Noyori, R. J. Am.
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(
1
970, 1420. (b) Grill, J. M.; Ogle, J. W.; Miller, S. A. J. Org.
Chem. 2006, 71, 9291.
(
11) (a) Morton, D.; Cole-Hamilton, D. J. J. Chem. Soc., Chem.
Commun. 1988, 1154. (b) Ligthart, G. B. W. L.; Meijer, R.
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J.; Gandelman, M.; Shimon, L. J. W.; Rozenberg, H.;
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Acknowledgment
The authors would like to thank Dr. Masahiro Kajino, Dr. Atsuhiko
Zanka, and Dr. David G. Cork for helpful discussions. We thank
Mr. Qingwei Zheng (Department of Chemistry, Tsinghua Universi-
ty) for his technical assistance.
(
f) van Buijtenen, J.; Meuldijk, J.; Vekemans, J. A. J. M.;
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References and Notes
2
(1) (a) Bowden, K.; Heilbron, I. M.; Jones, E. R. H.; Weedon, B.
C. L. J. Chem. Soc. 1946, 39. (b) Bowers, A.; Halsall, T. G.;
©
Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1438–1442

1442
N. Fukuda et al.
LETTER
(12) (a) Fujita, K.; Tanino, N.; Yamagchi, R. Org. Lett. 2007, 9,
the mixture was stirred for 20 min. The organic layer was
1
09. (b) Royer, A. M.; Rauchfuss, T. B.; Gray, D. L.
collected, washed with 1 N NaOH (50 mL) followed by H O
2
Organometallics 2010, 29, 6763. (c) Fujita, K.; Yoshida, T.;
Imori, Y.; Yamagchi, R. Org. Lett. 2011, 13, 2278.
13) Morton, D.; Cole-Hamilton, D. J. J. Chem. Soc., Chem.
Commun. 1987, 248.
(50 mL), and concentrated. To the concentrate was added
i-PrOH (50 mL), and the mixture was heated to 35–45 °C.
(
(
H O (25 mL) and seed crystals of 2a (10 mg) were added to
2
the mixture to initiate crystallization. Additional H O (125
2
14) (a) Cella, J. A.; Kelley, J. A.; Kenehan, E. F. J. Org. Chem.
mL) was added dropwise for over 1 h, and then the mixture
was stirred at 35–45 °C, 20–25 °C, and 0–10 °C, for over 1
h at each. The resultant crystals were collected by filtration,
1
975, 40, 1860. (b) Semmelhack, M. F.; Schmid, C. R.;
Cortés, D. A.; Chou, C. S. J. Am. Chem. Soc. 1984, 106,
374. (c) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. J.
3
washed with H O (50 mL), and dried under reduced pressure
2
1
Org. Chem. 1987, 52, 2559. (d) Anelli, P. L.; Banfi, S.;
Montanari, F.; Quici, S. J. Org. Chem. 1989, 54, 2970.
at 50 °C to provide 2a as white crystals (8.93 g, 90.3%). H
NMR (500 MHz, CDCl ): δ = 7.35–7.50 (m, 3 H), 7.58–7.64
3
(
e) Siedlecka, R.; Skarźewski, J.; Młochowski, J.
(m, 2 H), 7.69–7.75 (m, 2 H), 7.88–7.95 (m, 2 H), 10.03 (s,
1
3
Tetrahedron Lett. 1990, 31, 2177. (f) Leanna, M. R.; Sowin,
T. J.; Morton, H. E. Tetrahedron Lett. 1992, 33, 5029. (g) de
Nooy, A. E. J.; Besemer, A. C.; van Bekkurn, H. Synthesis
1 H). C NMR (125 MHz, CDCl ): δ = 127.4, 127.7, 128.5,
3
129.0, 130.3, 135.3, 139.7, 147.2, 191.9.
(22) Conditions: 2.3 or 2.4 equiv of NaOCl were used for these
reactions because the oxidations of some substrates with 1.8
equiv of NaOCl required longer reaction time.
(23) The Procedure for Oxidation to Carboxylic Acid
To a solution of 1f (1.00 g, 6.53 mmol) in DME (20 mL) was
added 10% aq NaOCl (11.67 g, 15.67 mmol) at r.t. The
1
996, 1153. (h) Einhorn, J.; Einhorn, C.; Ratajczak, F.;
Pierre, J.-L. J. Org. Chem. 1996, 61, 7452. (i) Mico, A. D.;
Margarita, R.; Parianti, L.; Vescovl, A.; Piancatelli, G. J.
Org. Chem. 1997, 62, 6974. (j) Rychnovsky, S. D.;
Vaidyanathan, R. J. Org. Chem. 1999, 64, 310. (k) Luca, L.
D.; Giacomelli, G.; Porcheddu, A. Org. Lett. 2001, 3, 3041.
mixture was stirred at r.t. for 4 h before adding 10% Na SO3
2
(
l) Shibuya, M.; Tomizawa, M.; Suzuki, I.; Iwabuchi, Y. J.
(10 mL). The mixture was adjusted to pH 3.5 with 6 M HCl
and extracted with EtOAc (20 mL). The aqueous layer was
extracted again with EtOAc (10 mL), and the combined
Am. Chem. Soc. 2006, 128, 8412. (m) Shibuya, M.; Sato, T.;
Tomizawa, M.; Iwabuchi, Y. Chem. Commun. 2009, 1739.
(
n) Shibuya, M.; Osada, Y.; Sasano, Y.; Tomizawa, M.;
organic extract was washed with H O (10 mL) before being
2
Iwabuchi, Y. J. Am. Chem. Soc. 2011, 133, 6497.
concentrated under reduced pressure. EtOAc (4 mL) and n-
(
15) (a) Shimizu, M.; Kuwajima, I. Tetrahedron Lett. 1979, 20,
heptane (4 mL) were added at r.t., then the solids were
2
801. (b) Shimizu, M.; Urabe, H.; Kuwajima, I. Tetrahedron
collected by filtration and washed with n-heptane (3 mL) to
1
Lett. 1981, 22, 2183. (c) Kuwajima, I.; Shimizu, M.; Urabe,
H. J. Org. Chem. 1982, 47, 837.
afford 3f (1.01 g, 93%). H NMR (500 MHz, DMSO-d ): δ
6
= 8.18 (d, J = 8.8 Hz, 2 H), 8.33 (d, J = 8.8 Hz, 2 H), 13.68
1
3
(
(
(
(
16) Mirafzal, G. A.; Lozeva, A. M. Tetrahedron Lett. 1998, 39,
(br s, 1 H). C NMR (125 MHz, DMSO-d ): δ = 123.6,
6
7
263.
17) Stevens, R. V.; Chapman, K. T. Tetrahedron Lett. 1982, 23,
647.
18) Ando, T.; Cork, D. G.; Fujita, M.; Kimura, T. Chem. Express
987, 2, 297.
130.6, 136.4, 150.0, 165.7.
(24) The Procedure for Oxidation of 1o
4
A mixture of 1o (500 mg, 2.74 mmol) and DME (10 mL) was
stirred at r.t. and then 10% aq NaOCl (4.90 g, 6.59 mmol)
was gradually added to the mixture. Stirring of the mixture
was continued at r.t. for 4 h. Then 10% aq Na SO (5 mL)
was added to the mixture, and stirring was continued for 5
min. EtOAc (20 mL) and H O (10 mL) were added to the
mixture. Quantitative analysis of the organic layer by HPLC
showed the yield of 2o to be 100%, and then the organic
layer was concentrated, and the residue was purified by
column chromatography on silica gel using n-hexane–
1
19) (a) Galvin, J. M.; Jacobsen, E. N. In Encyclopedia of
Reagents for Organic Synthesis; Vol. 7; Paquette, L. A., Ed.;
John Wiley and Sons: Chichester, 1995, 4580. (b) Banfi, S.;
Montanari, F.; Quici, S. J. Org. Chem. 1989, 54, 1850.
20) Meyers, C. Y. J. Org. Chem. 1961, 26, 1046.
21) General Procedure
2
3
2
(
(
A mixture of 1a (10 g, 54.3 mmol) and DME (100 mL) was
stirring at 20–30 °C, and 10% (w/w) NaOCl (72.7 g, 97.7
mmol; Wako Pure Chemical Industries, Ltd.) was gradually
added to the mixture at 20–25 °C. The reaction was
continued for 4 h while keeping the temperature at 20–25 °C.
After the reaction was completed, 5% aq Na S O (50 mL)
EtOAc (10:1) as eluent to provide the desired ketone 2o (492
1
mg, 99%). H NMR (500 MHz, CDCl ): δ = 7.17–7.27 (m, 2
3
1
3
H), 7.35–7.47 (m, 4 H), 7.54–7.63 (m, 2 H). C NMR (125
MHz, CDCl ): δ = 120.3, 124.2, 129.0, 134.1, 134.6, 144.3,
3
193.7.
2
2
3
and toluene (50 mL) were added to the reaction mixture, and
Synlett 2013, 24, 1438–1442
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