Mild oxidation of alcohols with o-iodoxybenzoic acid in liquid tetrabutylammonium bromide

Article abstract of DOI:10.14233/ajchem.2015.17046

A mild, green and low cost method for o-iodoxybenzoic acid mediated oxidation of alcohols to carbonyl compounds has been established. In this protocol, liquid tetrabutylammonium bromide was used as the solvent and the primary alcohols were selectively oxidized to aldehyde and secondary alcohols were easily transformed to ketones.

Full text of DOI:10.14233/ajchem.2015.17046

Asian Journal of Chemistry; Vol. 27, No. 2 (2015), 587-590
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2015.17046
Mild Oxidation of Alcohols with o-Iodoxybenzoic Acid in Liquid Tetrabutylammonium Bromide
*
YANGYANG LIU, AMING XIE, MEIPING CAO, LIANDONG FENG and BOLIANG WANG
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, P.R. China
*Corresponding author: Tel: +86 25 84315526-807; E-mail: boliangwang@njust.edu.cn
Received: 16 January 2014;
Accepted: 6 May 2014;
Published online: 10 January 2015;
AJC-16625
A mild, green and low cost method for o-iodoxybenzoic acid mediated oxidation of alcohols to carbonyl compounds has been established.
In this protocol, liquid tetrabutylammonium bromide was used as the solvent and the primary alcohols were selectively oxidized to
aldehyde and secondary alcohols were easily transformed to ketones.
Keywords: o-Iodoxybenzoic acid, Oxidation, Tetrabutylammonium bromide.
As an inexpensive common reagent, tetrabutylammonium
bromide (TBAB)21-23 has been used in many chemical reactions.
We24 previously reported that tetrabutylammonium bromide
was an efficient media for converting nitriles to 5-substituted
1H-tetrazoles. We present here a green and low-cost method
for the o-iodoxybenzoic acid mediated oxidation of alcohols
in liquid tetrabutylammonium bromide (Fig. 1).
INTRODUCTION
The oxidation of alcohols to carbonyl compounds is one
of the most fundamental process1,2 in organic chemistry.
Traditional methods have required the use of stoichiometric
oxidizing reagents, of which toxic transition metals3,4 were
most commonly used. Serious environmental concerns
prompted chemists to develop greener methods. Considerable
interest has been paid to using molecular oxygen or air as the
terminal oxidant5-7. However, this area is not mature and
furthermore, catalytic amount of heavy metals were still used
in the systems. Recently, Hu et al.8 and others9-12 have deve-
loped a transition metal free oxidation of alcohols utilizing
TEMPO-based catalyst systems.
IBX r.t.
O H
O
TBAB and Water
2
1
Fig. 1. o-Iodoxybenzoic acid (IBX) mediated oxidation of alcohols in liquid
tetrabutylammonium bromide (TBAB)
Last few years13-17 have seen a great deal of interest in
o-iodoxybenzoic acid and its oxidation ability of alcohols as
well as nitrogen-containing and sulfur-containing organic
compounds, which was often achieved in mild conditions, in
high yields and with high chemoselecticity. Because of poor
solubility of o-iodoxybenzoic acid in most organic solvents,
the process was often done in DMSO at slightly elevated tempe-
rature, which is practically the only solvent that dissolves o-
iodoxybenzoic acid18. Recently, several alternative procedures
have been introduced in the literature. Vinod and coworkers19
used a water/acetonitrile biphasic solvent system while Giannis
and Schulze20 used a water/ethyl acetate biphasic solvent system
with Bu4NHSO4 as phase-transfer catalyst. Zheng's group18
has developed a greener procedure which was achieved in ionic
liquid and water. However, the cost was increased by using
alkylated imidazoles. Therefore, it is highly desirable to develop
an environmentally friendly and economical process for the
oxidation of alcohols with o-iodoxybenzoic acid.
EXPERIMENTAL
All reagents were purchased from commercial suppliers
and used without further purification. NMR spectra obtained
with tetramethylsilane (TMS, δ = 0 ppm) as internal standard
in CDCl3 using a BrukerAvance 500 spectrometer (500 MHz)
or Bruker Avance 300 spectrometer (300 MHz).
General procedure: To a mixture of tetrabutylammonium
bromide (2 mmol, 0.64 g) and water (2 mL) was added o-
iodoxybenzoic acid and the corresponding alcohol 1 (2 mmol).
The reaction mixture was stirred at room temperature for 1 h.
After the reaction was complete, 10 mL water was added and
the liquid phase was extracted with diethyl ether. IBA was
recovered by filtration. The organic phase was washed with
water, dried over sodium sulfate and concentrated under
vacuum to give the pure product 2. The aquaous phase was
evaporated under vacuum and tetrabutylammonium bromide
was recovered.

588 Liu et al.
Asian J. Chem.
1
Acetophenone (2a)25, Table-1, entry 5: H NMR (300
MHz, CDCl3) δ 7.97 (m, 2H), 7.57 (m, 1H), 7.46 (m, 2H),
2.61 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 198.13, 136.97,
133.03, 128.47, 128.20, 26.49.
(dd, J = 7.7, 1.7 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 195.75,
140.63, 135.51, 135.05, 130.24, 128.74, 100.81.
4-Phenyl-2-butanone. (2l)30, Table-2, entry 12: 1H NMR
(300 MHz, CDCl3) δ 7.27 (m, 2H), 7.20 (t, J = 6.3 Hz, 2H),
2.89 (d, J = 7.2 Hz, 2H), 2.78 (d, J = 7.3 Hz, 2H), 2.15 (s, 3H).
13C NMR (75 MHz, CDCl3) δ 207.91, 140.93, 128.43, 128.23,
126.04, 45.08, 30.00, 29.65.
Propiophenone (2b)26, Table-2, entry 2: 1H NMR (300
MHz, CDCl3) δ 7.96 (m, 2H), 7.54 (d, J = 7.3 Hz, 1H), 7.46 (t,
J = 7.4 Hz, 2H), 3.01 (q, J = 7.2 Hz, 2H), 1.23 (t, J = 7.2 Hz,
3H). 13C NMR (75 MHz, CDCl3) δ 200.65, 136.79, 132.77,
128.45, 127.85, 31.65, 8.12.
1
2-Octanone (2m)30, Table-2, entry 13: H NMR (300
MHz, CDCl3) δ 2.41 (t, 2H), 2.13 (s, 3H), 1.56 (m, 2H), 1.27
(s, 6H), 0.87 (t, 3H). 13C NMR (75 MHz, CDCl3) δ 209.17,
43.63, 31.45, 29.66, 28.70, 23.67, 22.35, 13.86.
Cyclohexanone (2n)25, Table-2, entry 14: 1H NMR (300
MHz, CDCl3) δ 2.33 (m, 4H), 1.86 (m, 4H), 1.72 (m, 2H). 13C
NMR (75 MHz, CDCl3) δ 212.08, 41.81, 26.87, 24.82.
3'-Methoxyacetophenone (2c)27, Table-2, entry 3: H
1
NMR (300 MHz, CDCl3) δ 7.49 (m, 1H), 7.37 (t, 2H), 7.11
(m, 1H), 3.86 (m, 3H), 2.60 (s, 3H). 13C NMR (75 MHz, CDCl3)
δ 197.82, 159.68, 138.35, 129.46, 121.00, 119.46, 112.23,
55.28, 26.60.
4'-Methoxyacetophenone (2d)28, Table-2, entry 4: H
1
RESULTS AND DISCUSSION
NMR (300 MHz, CDCl3) δ 7.93 (m, 2H), 6.94 (m, 2H), 3.87
(s, 3H), 2.56 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 196.66,
163.37, 130.47, 130.18, 113.56, 55.34, 26.23.
We initiated our studies with the oxidation of 1-phenyl-
ethanol with o-iodoxybenzoic acid in water at 80 °C. Only
trace acetophenone formed after 10 h (Table-1, entry 1). Then
the reaction was carried out in molten tetrabutylammonium
bromide at 105 °C (Table-1, entry 2). The mixture soon turned
dark and no product was found, probably due to instability of
o-iodoxybenzoic acid at elevated temperature14.A small portion
of water was then added and the temperature was lowered to
80 °C and acetophenone was formed after 2 h and then isolated
in 55 % (Table-1, entry 3). Encouraged by the result, we lowered
the temperature again, hopefully the reaction could proceed
at room temperature (Table-1, entry 4). Because such attempt
was in vain, we next increased the amount of water by 10-fold
(Table-1, entry 5). To our delight, the reaction proceeded
smoothly and excellent yield was obtained. Further increase
of the amount of water was detrimental to the yield (Table-1,
entry 6 and 7).
1
Benzaldehyde (2e)25, Table-2, entry 5: H NMR (500
MHz, CDCl3) δ 10.05 (s, 1H), 7.90 (m, 2H), 7.66 (m, 1H),
7.56 (t, J = 7.6 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 192.26,
134.35, 129.62, 128.90.
2-Methoxybenzaldehyde (2f)25, Table-2, entry 6: H
1
NMR (300 MHz, CDCl3) δ 10.48 (s, 1H), 7.85 (m, 1H), 7.57
(m, 1H), 7.02 (m, 2H), 3.94 (s, 3H). 13C NMR (75 MHz, CDCl3)
δ 189.69, 161.74, 135.88, 128.37, 124.71, 120.54, 111.55,
55.52.
3-Methoxybenzaldehyde (2g)25, Table-2, entry 7: H
1
NMR (300 MHz, CDCl3) δ 9.98 (s, 1H), 7.47 (m, 2H), 7.40 (s,
1H), 7.19 (m, 1H), 3.87 (s, 3H). 13C NMR (75 MHz, CDCl3) δ
191.96, 160.00, 137.68, 129.89, 123.24, 121.22, 112.02, 55.23.
4-Methoxybenzaldehyde (2h)25, Table-2, entry 8: H
1
NMR (500 MHz, CDCl3) δ 9.90 (s, 1H), 7.85 (d, J = 8.3 Hz,
2H), 7.02 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H). 13C NMR (126
MHz, CDCl3) δ 190.77, 164.60, 131.94, 129.93, 114.30, 55.53.
4-Formylbenzonitrile (2i)29, Table-2, entry 9: 1H NMR
(300 MHz, CDCl3) δ 10.10 (s, 1H), 8.00 (m, 2H), 7.85 (d,
2H). 13C NMR (75 MHz, CDCl3) δ 190.62, 138.65, 132.82,
129.81, 117.65, 117.47.
4-Nitrobenzaldehyde (2j)25, Table-2, entry 10: 1H NMR
(300 MHz, CDCl3) δ 10.17 (s, 1H), 8.40 (d, J = 8.5 Hz, 2H),
8.08 (d, J = 8.6 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 190.34,
150.98, 139.97, 130.41, 124.19.
Having optimized the reaction conditions, we next
explored the scope of this reaction. The results were shown in
Table-2. All primary alcohols were oxidized into aldehyde
while no further oxidation was found and secondary alcohols
were easily transformed into ketones. It was found that benzyl
alcohols generally proceeded well while alkyl alcohols
generally were obtained in moderate yield. This phenomenon
is in accordance with the literature14. Electron-donating groups
introduced at o-, m- and p-position of the benzyl alcohols all
furnished the corresponding product, although slightly better
yield was obtained with those introduced at p-position
(Table-2, entries 3, 4, 6-8). In contrast, only low to moderate
yield was obtained with benzyl alcohols bearing strong
2-Iodobenzaldehyde (2k)30, Table-2, entry 11: 1H NMR
(300 MHz, CDCl3) δ 10.08 (s, 1H), 7.97 (d, J = 7.9 Hz, 1H),
7.89 (dd, J = 7.7, 1.7 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 7.31
TABLE-1
REACTION OF OPTIMIZATION OF o-IODOXYBENZOIC ACID MEDIATED OXIDATION OF 1-PHENYLETHANOL TO 2aa
Entry
Temperature (°C)
80
Solventb
Waterd
Time (h)
Yield (%)c
1
2
3
4
5
6
7
10
1
Trace
-
105
TBAB
80
10:1 TBAB-Water (mol/mol)
10:1 TBAB-Water (mol/mol)
10:10 TBAB-Water (mol/mol)
10:20 TBAB-Water (mol/mol)
10:40 TBAB-Water (mol/mol)
1
55
Room temperature
Room temperature
Room temperature
Room temperature
1
Trace
92
1
1
87
1
85
aOxidation of alcohols (2 mmol 1 equiv) was conducted with o-iodoxybenzoic acid (2.2 mmol, 1.1 equiv), bTBAB(2 mmol) was used,
cIsolated yield, d Only water was used

Vol. 27, No. 2 (2015)
Mild Oxidation of Alcohols with o-Iodoxybenzoic Acid in Liquid Tetrabutylammonium Bromide 589
TABLE-2
SUBSTRATE SCOPE OF o-IODOXYBENZOIC ACID MEDIATED
to o-iodoxybenzoic acid by oxone. The regenerated o-iodoxy-
benzoic acid was reused and no difference was found from a
freshly prepared one (Table-3, entry 4). tetrabutylammonium
bromide was also recovered by evaporation under vacuum and
reused without obvious decrease of the yields of products
(Table-3).
OXIDATION OF 1-PHENYLETHANOL TO 2aa
Entry
1
Substrate
Product
2a
Yield (%)b
OH
92
TABLE-3
RESULTS OBTAINED USING RECYCLED
TETRABUTYLAMMONIUM BROMIDE (TBAB)
2
2b
91
Yield (%)a
OH
Entry
Substrate
Cycle
OH
1
2
3
4
1
92
O
3
4
OH
2c
2d
93
96
OH
OH
OH
2
3
4
92
91
OH
O
OH
5
6
7
8
9
2e
2f
90
91
92
95
61
OH
91b
O
O
aIsolated yields based on 1-phenylethanol, bRecycled o-iodoxybenzoic
acid was used
OH
2g
2h
2i
OH
OH
OH
Conclusion
O
We presented here a mild, efficient, low cost and environ-
mentally friendly method for o-iodoxybenzoic acid mediated
oxidation of alcohols using the inexpensive liquid tetrabutyl-
ammonium bromide as solvent. Secondary alcohols were easily
oxidized to ketones and primary alcohols were transformed
to aldehyde while no further oxidation products were found.
The side product emerged and solvent used can be recycled.
NC
10
11
2j
59
61
O2N
OH
2k
REFERENCES
I
OH
1.
K. Mori, T. Hara, T. Mizugaki, K. Ebitani and K. Kaneda, J. Am. Chem.
Soc., 126, 10657 (2004).
12
2l
79
2. K. Bowden, I.M. Heilbron, E.R.H. Jones and B.C.L. Weedon, J. Chem.
Soc., 39 (1946).
3. E.J. Corey and J.W. Suggs, Tetrahedron Lett., 16, 2647 (1975).
4. E.J. Corey and C.U. Kim, J. Am. Chem. Soc., 94, 7586 (1972).
5. H. Tomioka, K. Takai, K. Oshima and H. Nozaki, Tetrahedron Lett.,
22, 1605 (1981).
OH
13
14
2m
2n
65
77
OH
6. I.E. Markó, P.R. Giles, M. Tsukazaki, S.M. Brown and C.J. Urch, Science,
274, 2044 (1996).
7. T. Mallat and A. Baiker, Chem. Rev., 104, 3037 (2004).
8. R. Liu, X. Liang, C. Dong and X. Hu, J. Am. Chem. Soc., 126, 4112
(2004).
aOxidation of alcohols (2 mmol 1 equiv.) was conducted with o-iodo-
xybenzoic acid (2.2 mmol, 1.1 equiv.) in TBAB (2 mmol) and water (2
mmol) in 1 h; bIsolated yields
9. B. Karimi, A. Biglari, J.H. Clark and V. Budarin, Angew. Chem. Int.
Ed., 46, 7210 (2007).
10. X. Wang, R. Liu, Y. Jin and X. Liang, Chem. Eur. J., 14, 2679 (2008).
11. Y. Xie, W. Mo, D. Xu, Z. Shen, N. Sun, B. Hu and X. Hu, J. Org. Chem.,
72, 4288 (2007).
electron-withdrawing groups, indicating the limitations of the
reaction (Table-2, entries 9,10). Strong steric hindrance of o-
substituents such as an iodo-group did not deter the desired
oxidation from occurring (Table-2, entry 11).
12. M. Shibuya, Y. Osada, Y. Sasano, M. Tomizawa and Y. Iwabuchi, J. Am.
Chem. Soc., 133, 6497 (2011).
13. K.C. Nicolaou, P.S. Baran,Y. Zhong, S. Barluenga, K.W. Hunt, R. Kranich
and J.A. Vega, J. Am. Chem. Soc., 124, 2233 (2002).
14. K.C. Nicolaou, T. Montagnon, P.S. Baran and Y. Zhong, J. Am. Chem.
Soc., 124, 2245 (2002).
Iodosobenzylic acid (IBA), the side product of o-iodoxy-
benzoic acid mediated oxidation, could be easily recovered
by simple filtration after water was added and then reoxidized

590 Liu et al.
Asian J. Chem.
15. K.C. Nicolaou, C.J.N. Mathison and T. Montagnon, J. Am. Chem. Soc.,
126, 5192 (2004).
24. A. Xie, M. Cao, L. Feng and W. Dong, J. Chem. Res., 37, 665 (2013).
25. C. Miao, L. He, J. Wang and F. Wu, J. Org. Chem., 75, 257 (2010).
26. R. Chorghade, C. Battilocchio, J.M. Hawkins and S.V. Ley, Org. Lett.,
15, 5698 (2013).
16. A. Duschek and S.F. Kirsch, Angew. Chem. Int. Ed., 50, 1524 (2011).
17. A.P. Thottumkara and T.K. Vinod, Tetrahedron Lett., 43, 569 (2002).
18. Z. Liu, Z. Chen and Q. Zheng, Org. Lett., 5, 3321 (2003).
19. A.P. Thottumkara, M.S. Bowsher and T.K. Vinod, Org. Lett., 7, 2933
(2005).
27. G. Zhang and S.K. Hanson, Org. Lett., 15, 605 (2013).
28. R. Kawahara, K.- Fujita and R. Yamaguchi, J. Am. Chem. Soc., 134,
3643 (2012).
20. A. Schulze and A. Giannis, Synthesis, 257 (2006).
21. B.C. Ranu, A. Das and S. Samanta, J. Chem. Soc., Perkin Trans. 1,
1520 (2002).
29. S. Korsager, R.H. Taaning, A.T. Lindhardt and T. Skrydstrup, J. Org.
Chem., 78, 6112 (2013).
30. J.E. Steves and S.S. Stahl, J. Am. Chem. Soc., 135, 15742 (2013).
22. B.C. Ranu and S.S. Dey, Tetrahedron Lett., 44, 2865 (2003).
23. I. González, S. Bouquillon, A. Roglans and J. Muzart, Tetrahedron Lett.,
48, 6425 (2007).