Chloramine-T-mediated oxidation of benzylic alcohols using indium(III) triflate

Article abstract of DOI:10.1248/cpb.c17-00061

The efficient oxidation of benzylic alcohols to carbonyl compounds was performed using chloramine-T and a catalytic amount of indium(III) triflate. The primary benzylic alcohols were converted to the corresponding aldehydes in a good yield, and the secondary benzylic alcohols were oxidized to ketones in a high yield. The optimized reaction conditions required 0.3eq of indium(III) triflate and the use of acetonitrile as a solvent.

Full text of DOI:10.1248/cpb.c17-00061

Vol. 65, No. 8
Chem. Pharm. Bull. 65, 801–804 (2017)
801
Note
Chloramine-T-Mediated Oxidation of Benzylic Alcohols Using
Indium(III) Triflate
Kazuhide Nakahara, Chie Kitazawa, and Tomoko Mineno*
Laboratory of Medicinal Chemistry, Faculty of Pharmacy, Takasaki University of Health and Welfare; 60 Nakaorui,
Takasaki, Gunma 370–0033, Japan.
Received January 18, 2017; accepted May 25, 2017
The efficient oxidation of benzylic alcohols to carbonyl compounds was performed using chloramine-T
and a catalytic amount of indium(III) triflate. The primary benzylic alcohols were converted to the corre-
sponding aldehydes in a good yield, and the secondary benzylic alcohols were oxidized to ketones in a high
yield. The optimized reaction conditions required 0.3eq of indium(III) triflate and the use of acetonitrile as
a solvent.
Key words oxidation; alcohol; chloramine-T; indium(III) triflate
The oxidation of alcohol moieties to the corresponding
The oxidation of alcohols using metal-based reagents that
carbonyl compounds is common in the field of organic syn- include manganese,4,5) ruthenium,6) copper,7) chromium,8,9)
thesis. Various reagents and reactions have been reported in and palladium10,11) have been reported, but these are reac-
the oxidative reactions of alcohols.1) Particularly, two methods, tions using heavy transition metals, which are not considered
Swern oxidation2) and Dess–Martin oxidation3) have been environmentally friendly, at times. Therefore, our study was
mainstays in organic and medicinal syntheses for decades.
focused on an oxidative reaction of alcohols that could be per-
When primary alcohols are subjected to Swern oxidation, formed using an indium reagent instead of transition metals,
they are transformed to the corresponding aldehydes, and the keeping with the latest trends toward more environmentally
oxidation does not progress further to yield carboxylic acids. green chemistry. We have studied the catalyst effect of indium
In Swern oxidation, however, the active intermediate derived reagents for past several years, and have reported various
from dimethyl sulfoxide and oxalyl chloride is thermally chemical transformations using them.12–15)
unstable, and strict control of the reaction temperature is re-
Also, there exists a precedent study of selective oxidation of
quired. Swern oxidation can be coupled with the generation of primary alcohols that results only the corresponding aldehyde
toxic carbon monoxide and dimethyl sulfide, which makes this compounds without the indication of over-oxidation to the car-
reaction unsuitable for large-scale synthesis. Meanwhile, the boxylic acids. The study must be a suitable evidence for the
reagent used in Dess–Martin oxidation includes a hypervalent compatibility of chloramine-T and transition metal catalyst.16)
state of iodine. Therefore, cautious treatment is required due Another precedent notable study includes sulfonamide cata-
to the risk that is magnified by increases in the reaction scale. lyzed oxidation of alcohols using chloramine-T derivatives.
Thus, this reagent must be handled with great care.
It is noteworthy that the oxidation was applicable not only
Table 1. Reactions during the Search for Optimal Conditions
*To whom correspondence should be addressed. e-mail: mineno@takasaki-u.ac.jp
© 2017 The Pharmaceutical Society of Japan

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Vol. 65, No. 8 (2017)
Table 2. The Oxidation of Primary Benzylic Alcohols Using In(OTf)3 as a Lewis Acid
to benzylic alcohols but also to aliphatic alcohols, such as
With the optimal conditions for the oxidation of alcohols in
2-methylpentanol or octanol, with high yields.17) Based on the hand, we next examined applicability. Various primary ben-
outcome from our continuous research, we have attempted to zylic alcohols, phenylmethanol analogues, were subjected to
elucidate that the starting benzylic alcohols could be subjected the reaction using a 0.3eq of indium(III) triflate with CH3CN
to a reaction with chloramine-T in order to be converted to as a solvent, as shown in Table 2 (entries 1, 2, 3, and 4).22–25)
the corresponding aldehyde or ketone functionalities by using The reactions proceeded and generated the corresponding
indium(III) triflate as a Lewis acid. Herein, we wish to de- aldehyde compounds in 50–70% yields with no major per-
scribe the details of our study.
ceptible byproduct, which could be due to the untoward de-
composition occurring after the generation of newly formed
aldehydes.
Results and Discussion
Using 1mmol of 1-(para-tolyl)ethanol as the starting sub-
In further studies, secondary benzylic alcohols were used
strate, we strived to find the optimal conditions for an oxida- under the optimized oxidation reaction conditions. As shown
tion reaction, as presented in Table 1.18) Several commercially in Table 3, these reactions proceeded smoothly to give the cor-
available indium salts were tested, and indium(III) triflate responding carbonyl compounds in good to high yields. The
proved to be the most efficient Lewis acid when CH3CN first attempt was the oxidation of the isomers of the methyl
was used as a solvent (entries 1, 2, and 3). The entries using group at the meta-position which afforded a high yield, as the
CH3CN as the solvent afforded the expected product, whereas isomer with a methyl substituent at the para-position resulted
the entries using solvents such as toluene, CH2Cl2, and tetra- in the higher yield (entries 1 and 2).18) Thus, the influence of
hydrofuran (THF), all resulted in no reaction (entries 1, 4, 5, the substituents at the meta and para positions was minimized
and 6). On the other hand, we have reported useful method- in this case. Also, the oxidation of alcohols with a propanol
ologies focused on indium(III) triflate using solvents such as moiety showed good results (entries 3 and 4).26,27) Further-
CH2Cl2, THF, or MeOH, and thus these outcomes in terms of more, this process was extended to compounds with two
solvents need not to deny the compatibility of Lewis acids and aromatic rings, and oxidation reactions starting with diphe-
solvents.19–21)
nylmethanol analogues were carried out.28–31) These reactions
The use of a 0.3eq of indium(III) triflate was discovered proceed smoothly to give the corresponding diphenylketone
to be one of the key factors for the optimal reaction condition compounds in excellent yields. The electron-donating and
(entries 1, 7, 8, and 9). The reaction without Lewis acid gave electron-withdrawing substituents, such as halogens on the
a yield of 37% (entry 9), and thus the presence of indium(III) benzene ring, did not significantly influence the reaction ef-
triflate must contribute for smooth reactions based on the pre- ficacy of the diphenylmethanol analogues (entries 5, 6, 7, 8,
viously suggested reaction mechanism in a similar manner.16) and 9). However, the electron-donating methoxy group, where
Attempts that avoid the use of a stoichiometric amount of the oxygen atom can withdraw electron density inductively, at
chloramine-T resulted in no reaction, as predicted (entry 10). the para-position gave a reduced yield of 52% (entry 10).32,33)
As a result, the maximum yield of the oxidation product was Furthermore, comparison of entries 4 and 11 could suggest
obtained by pairing a 0.3eq of indium(III) triflate as a Lewis the steric hindrance of methyl group at the ortho-position was
acids with CH3CN as a solvent (entry 8).
quite significant.34,35)

Vol. 65, No. 8 (2017)
Chem. Pharm. Bull.
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Table 3. The Oxidation of Secondary Benzylic Alcohols Using In(OTf)3 as a Lewis Acid
out purification. All reactions were carried out under an argon
Conclusion
In conclusion, we established an efficient method for the atmosphere using magnetic stirring unless otherwise noted.
oxidation of benzylic alcohols to aldehydes or ketones in the 1H-NMR and 13C-NMR spectral data were recorded on JEOL
presence of a stoichiometric amount of chloramine-T with a JMTC-500 spectrometer using TMS as an internal standard.
catalytic amount of indium(III) triflate. Many primary and
General Experimental Procedure The starting 1-(para-
secondary benzylic alcohols were applied to the optimized tolyl)ethanol (1mmol), chloramine-T (1mmol), and In(OTf)3
reaction conditions, and these furnished the corresponding (0.3mmol) were dissolved in CH3CN (10mL) in a 100mL
carbonyl compounds in good to excellent yields. The reaction flask equipped with a magnetic stirrer and a reflux condenser.
conditions were sufficiently mild and yielded only the expect- The reaction mixture was heated at reflux for 3h under an
ed products with no major byproducts.
Argon atmosphere and was monitored for completion by TLC.
After the reaction mixture was cooled to room temperature,
the solvent was removed via rotary evaporation. The residue
Experimental
Materials and Instruments All reagents were of analyti- of the reaction mixture was separated through flash column
cal grade. These were purchased commercially and used with- chromatography on silica gel. The obtained product was con-

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Lett., 54, 533–535 (2013).
Vol. 65, No. 8 (2017)
firmed by spectroscopy.
17) Kitagawa H., Mukaiyama T., Chem. Pharm. Bull., 50, 1276–1279
(2002).
Acknowledgment We are thankful to Dr. H. Kansui (Sojo
18) Budesinsky M., Kulhanek J., Bohm S., Cigler P., Exner O., Magn.
Reson. Chem., 42, 844–851 (2004).
University) for his helpful suggestions.
19) Mineno T., Nikaido N., Kansui H., Chem. Pharm. Bull., 57, 1167–
1170 (2009).
Conflict of Interest The authors declare no conflict of
interest.
20) Mineno T., Sakai M., Ubukata A., Nakahara K., Yoshimitsu H.,
Kansui H., Chem. Pharm. Bull., 61, 870–872 (2013).
21) Mineno T., Tsukagoshi R., Iijima T., Watanabe K., Miyashita H.,
Yoshimitsu H., Tetrahedron Lett., 55, 3765–3767 (2014).
22) Lee K., Maleczka R. E. Jr., Org. Lett., 8, 1887–1888 (2006).
23) Iinuma M., Moriyama K., Togo H., Tetrahedron, 69, 2961–2970
(2013).
24) Yeung P. Y., So C. M., Lau C. P., Kwong F. Y., Org. Lett., 13,
648–651 (2011).
25) Gooßen L. J., Khan B. A., Fett T., Treu M., Adv. Synth. Catal., 352,
2166–2170 (2010).
References
1) Larock R. C., “Comprehensive Organic Transformations, A Guide
to Functional Group Preparations,” 2nd Ed., John Wiley & Sons,
Inc., 1999, New York.
2) Huang S. L., Omura K., Swern D., J. Org. Chem., 41, 3329–3331
(1976).
3) Dess D. B., Martin J. C., J. Org. Chem., 48, 4155–4156 (1983).
4) Arrad O., Sasson Y., J. Org. Chem., 54, 4993–4998 (1989).
5) Menger F. M., Lee C., J. Org. Chem., 44, 3446–3448 (1979).
6) Morris P. E. Jr., Kiely D. E., J. Org. Chem., 52, 1149–1152 (1987).
7) Semmelhack M. F., Schmid C. R., Cortes D. A., Chou C. S., J. Am.
Chem. Soc., 106, 3374–3376 (1984).
26) Zhao B., Lu X., Tetrahedron Lett., 47, 6765–6768 (2006).
27) Katrizky A. R., Le K. N. B., Khelashvili L., Mohapatra P. P., J.
Org. Chem., 71, 9861–9864 (2006).
8) Poos G. I., Arth G. E., Beyler R. E., Sarett L. H., J. Am. Chem.
Soc., 75, 422–429 (1953).
28) Rao M. L. N., Venkatesh V., Dasgupta P., Tetrahedron Lett., 51,
4975–4980 (2010).
9) Luchiano Lombardo, Orgnic Syntheses, 1987, 65, 81–89.
10) Nagashima H., Tsuji J., Chem. Lett., 10, 1171–1172 (1981).
11) Blackburn T. F., Schwartz J., J. Chem. Soc., Chem. Commun., 1977,
157–158 (1977).
29) Jeon K. O., Jun J. H., Yu J. S., Lee C. K., J. Heterocycl. Chem., 40,
763–771 (2003).
30) Xing D., Guan B., Cai G., Fang Z., Yang L., Shi Z., Org. Lett., 8,
693–696 (2006).
12) Mineno T., Tsukagoshi R., Iijima T., Watanabe K., Miyashita H.,
Yoshimitsu H., Tetrahedron Lett., 55, 3765–3767 (2014).
13) Mineno T., Shinada M., Watanabe K., Yoshimitsu H., Miyashita H.,
Kansui H. International, J. Org. Chem., 4, 1–6 (2014).
14) Mineno T., Takebe Y., Tanaka C., Mashimo S. International, J. Org.
Chem., 4, 169–173 (2014).
15) Mineno T., Yoshino S., Ubukata A., Green and Sustainable Chemis-
try, 4, 20–23 (2014).
16) Wang P., Cai J., Yang J., Sun C., Li L., Hu H., Ji M., Tetrahedron
31) Rao M. L. N., Venkatesh V., Banerjee D., Tetrahedron, 63, 12917–
12926 (2007).
32) Cunningham A., Mokal-Parekh V., Wilson C., Woodward S., Org.
Biomol. Chem., 2, 741–748 (2004).
33) Penner G. H., Wasylishen R. E., Can. J. Chem., 67, 525–534 (1989).
34) Budhram R. S., Palaniswamy V. A., Eisenbraun E. J., J. Org.
Chem., 51, 1402–1406 (1986).
35) Uyanik M., Suzuki D., Yasui T., Ishihara K., Angew. Chem. Int. Ed.,
50, 5331–5334 (2011).