Oxidation of benzoins to benzoic acids using sodium hydride under oxygen atmosphere

Article abstract of DOI:10.1016/j.tetlet.2010.11.079

A facile oxidation of benzoins 1 to benzoic acids 2 using sodium hydride under oxygen atmosphere has been developed.

Full text of DOI:10.1016/j.tetlet.2010.11.079

Tetrahedron Letters 52 (2011) 502–504
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Oxidation of benzoins to benzoic acids using sodium hydride under
oxygen atmosphere
Sunhae Kang a, , Cheonik Joo a, , Sun Min Kim b, Hogyu Han a, , Jung Woon Yang b,
⇑
⇑
a Department of Chemistry, Korea University, Seoul 136-701, South Korea
b Department of Energy Science, Sungkyunkwan University, Suwon 440-746, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile oxidation of benzoins 1 to benzoic acids 2 using sodium hydride under oxygen atmosphere has
been developed.
Received 31 October 2010
Accepted 15 November 2010
Available online 18 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Oxidation of benzoins and benzils to benzoic acids has been
accomplished by using various oxidizing agents. Some of the
oxidants used in such transformation are hydroxylamine-O-
sulfonic acid,1 calcium hypochlorite,2 (diacetoxyiodo)benzene,3
chromyl trifluoroacetate,4 sodium percarbonate,5 electrogenerated
periodate,6 potassium iodide/sodium cyanide in methanol,7 potas-
sium peroxymonosulfate,8 air/hypervalent iodine(V) in water,9
sodium hypochlorite,10 periodic acid/bis(trimethylsilyl)chromate,11
ammonium persulfate in aqueous media,12 and silica-supported
sodium metaperiodate.13 In addition, oxidative cleavage of
of 1a was carried out under oxygen atmosphere. On the other
hand, the lower chemical yield (61%) of 2a was obtained even after
23 h when the reaction of 1a was performed in undegassed dry
NaH (2 equiv)
OH
O2 (1 atm)
O
O
Ar'
+
Ar
THF, 25 °C
Ar
OH
HO
Ar'
O
2
2'
1
a
-ketols and related ketones was achieved by using alkaline
hydrogen peroxide,14 alkali triperoxovanadate(V) trihydrates,15
and hydrogen peroxide/Na2WO4.16 However, despite their power-
ful efficiency for such oxidation, most of them are toxic and haz-
ardous metal materials and sometimes they produce by-products
such as aldehydes.
a. Ar = Ar' = Ph
f. Ar = Ar' = 3-ClC6H4
g.
b.
Ar = Ar' = 2-Naphthyl
Ar = Ar' = 4-ClC6H4
c. Ar = Ar' = 3-MeOC6H4
h. Ar = Ar' = 2-Thienyl
d.
e.
i.
Ar = Ph, Ar' = 4-ClC6H4
j. Ar = Ar' = C6H5CH2CH2
Ar = Ar' = 4-MeOC6H4
Ar = Ar' = 4-FC6H4
Very recently, we reported that the oxidation of benzoins using
2 equiv of NaH in THF gave the corresponding benzils in good to
excellent yields within 6–90 min at 0 or 25 °C.17 In our continuing
study of this reaction, we discovered that benzils thus produced
are further oxidized to benzoic acids when the reaction time is pro-
longed. Here, we report that the oxidation of benzoins to benzoic
acids via benzils using sodium hydride in THF is effectively pro-
moted under oxygen atmosphere. This new mild cascade oxidation
with the combined use of sodium hydride and molecular oxygen is
also found to be useful for the conversion of aliphatic acyloins to
the corresponding carboxylic acids in a similar manner.
To develop a useful protocol, we studied the oxidation of ben-
zoin 1a to benzoic acid 2a using 2.0 equiv of NaH in THF at room
temperature under a variety of conditions. First, we investigated
the effect of molecular oxygen. The high chemical yield (85%) of
the desired product 2a was obtained within 1 h when the reaction
Scheme 1. Oxidation of benzoins
1 to benzoic acids 2 using NaH under O2
atmosphere.
Table 1
Oxidation of benzoins 1 to benzoic acids 2 using NaH under O2 atmosphere
Entry
Substratea
Productb
Temp (°C)
Time (min)
Yieldc (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
2a
2b
2c
2d
2e
2f
25
25
25
25
25
25
25
25
25
25
60
30
60
120
30
10
10
45
30
300
85
80
72
45
74
66
79
67
77/76
47
2g
2h
2a/20g
2j
10
1j
a
⇑
Substrates 1b, 1c, 1e–1g, and 1j were prepared and characterized as
Corresponding authors. Tel.: +82 2 3290 3134; fax: +82 2 3290 3121 (H.H.), tel.:
+82 31 299 4276; fax: +82 31 299 4279 (J.W.Y.).
described.18
b
Products 2 were obtained and characterized as described.19
Isolated yield.
E-mail addresses: hogyuhan@korea.ac.kr (H. Han), jwyang@skku.edu (J.W. Yang).
These two authors contributed equally to this work.
c
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.079

S. Kang et al. / Tetrahedron Letters 52 (2011) 502–504
503
NaH
OH
Na O
Ar
O
O H
Ar'
O
O
O
(1 equiv)
Ar'
Ar'
Ar'
+
HO2
Ar
Ar
Ar
H
O
O
O
5
O2
1
3
4
6
NaH
(partial)
2 NaOH
O
NaH
O
O
O
O
O
(1 equiv)
2 HCl
2 + 2'
+
Ar
O
Ar'
+
OH
Ar
O
O
Ar'
Ar
O
Ar'
OH
9
9'
8
7
Figure 1. Proposed mechanism for the oxidation of benzoins 1 to benzoic acids 2 using NaH under O2 atmosphere.
THF under argon atmosphere. This result indicates that molecular
oxygen plays a key role in terms of the rate and the chemical yield.
For further optimization of the reaction condition, the loading of
sodium hydride was investigated. The variation of the NaH loading
(2.0 or 3.0 equiv) had no pronounced effect on the chemical yield.
After short screening of reaction parameters, we found that the
oxidation of benzoin using 2.0 equiv of NaH in THF at room tem-
perature under O2 (1 atm) furnished the desired benzoic acid in
high yield.
with an additional equiv of NaH. Finally, two carboxylic acids 2 and
20 are obtained as the desired products after acidic work-up.
To verify that hydroperoxide is released from the intermediate
3 and then involved in the subsequent oxidative cleavage of con-
comitantly produced benzil, we performed separate control exper-
iments.20 First, we ran the experiment with benzil 4a and an
external source of hydroperoxide. Consistent with our proposed
mechanism, benzoic acid 2a was obtained under this condition.
Thus, it is evident that hydroperoxide is indeed involved in the oxi-
dation of benzoins 1 to benzoic acids 2 through its nucleophilic at-
tack on benzils 4. We also attempted the oxidative cleavage of
benzils 4a and 4g using NaH under O2 atmosphere. However, these
benzils remained intact without forming benzoic acids 2a and 2g
even after 20 h under such condition. This is due to the lack of
hydroperoxide required for the oxidative cleavage of benzils when
the reaction using NaH and O2 started directly from benzils instead
of benzoins. Unlike benzoins 1, benzils 4 are unable to afford the
intermediate 3 needed for generating hydroperoxide in situ when
treated with NaH under O2 atmosphere (see Fig. 1). Accordingly,
it seems obvious that hydroperoxide, which is involved in the oxi-
dative cleavage of benzils 4, is released from the intermediate 3,
which is formed by reaction of benzoins 1 with NaH under O2
atmosphere. Taken together, an internal source of hydroperoxide
is proven to be produced upon oxidation of benzoins 1 to benzils
4 and responsible for the oxidative cleavage of benzils 4 to benzoic
acids 2 in the presence of NaH and O2.
With the optimized reaction conditions in hand, we then ex-
plored the cascade oxidation of several symmetrical and an
unsymmetrical benzoin derivatives possessing electron-donating
and -withdrawing substituents on the aromatic rings (Scheme 1
and Table 1).18,19 Benzoin 1a and naphthoin 1b were oxidized to
the corresponding carboxylic acids 2a and 2b in 85% and 80% yields
within 1 h and 0.5 h, respectively (Table 1, entries 1 and 2). Ben-
zoin derivatives 1c and 1d bearing the methoxy group at meta-
and para-positions were oxidized to the desired products 2c and
2d in 72% and 45% yields after 1 h and 2 h, respectively (Table 1,
entries 3 and 4). Thus, the chemical yield and the rate increase
with its decreasing electron-donating ability. In the case of benzoin
derivatives 1e–g bearing fluoro- or chloro-substituents at
meta- and para-positions, the desired products 2e–g were obtained
in 66–79% yields within 10–30 min (Table 1, entries 5–7). In
general, it turns out that the reaction rate becomes faster by
electron-withdrawing substituents, but becomes slower by
electron-donating substituents. Thenoin 1h containing the hetero-
aryl unit was also oxidized to thiophenecarboxylic acid 2h in 67%
yield within 45 min (Table 1, entry 8). In addition, the unsymmet-
rical benzoin derivative 1i was oxidatively cleaved to give an equal
amount of benzoic acid 2a (77% yield) and 4-chlorobenzoic acid 20g
(76% yield) within 30 min (Table 1, entry 9). Aliphatic acyloin 1j
was also oxidized to the corresponding carboxylic acid 2j in 47%
yield after 5 h (Table 1, entry 10).
In conclusion, we conducted a facile oxidation of benzoins to
benzoic acids via benzils using sodium hydride under oxygen
atmosphere in high yields. Hydroperoxide appears to play a vital
role as a driving force in this cascade reaction. Molecular oxygen
effects its formation, thereby enabling the simple control of this
cascade reaction. Further applications of this approach are cur-
rently underway in our laboratories.
The proposed mechanism for the sodium hydride and molecular
oxygen-mediated oxidation of benzoins 1 to benzoic acids 2 is
illustrated in Figure 1.7,15 The reaction pathway begins by the
deprotonation of the hydroxyl group of benzoins 1 with 1 equiv
Acknowledgments
This work was supported by the NRF grant (No. 2010-0022070)
to H.H. and the NRF WCU program (R31-2008-000-10029-0) to
J.W.Y.
of NaH.
molecular oxygen then takes place to liberate
hydroperoxide 5. The resulting -diketone is susceptible to nucle-
a-Hydride transfer from the resulting intermediate 3 to
a-diketone 4 and
a
References and notes
ophilic attack by hydroperoxide, thus generating the tetrahedral
intermediate 6. Anhydride 7 is thereupon formed presumably via
1,2-insertion of the negative oxygen to the neighboring carbonyl
group and simultaneous elimination of hydroxide. Subsequent
nucleophilic addition of hydroxide to anhydride gives the interme-
diate 8, which furnishes two carboxylates 9 and 90 upon treatment
1. Carter, K. N.; Hulse, J. E., III J. Org. Chem. 1982, 47, 2208–2210.
2. Nwaukwa, S. O.; Keehn, P. M. Tetrahedron Lett. 1982, 23, 3135–3138.
3. Podolešov, B. J. Org. Chem. 1984, 49, 2644–2646.
4. Suggs, J. W.; Ytuarte, L. Tetrahedron Lett. 1986, 27, 437–440.
5. Yang, D. T. C.; Evans, T. T.; Yamazaki, F.; Narayanna, C.; Kabalka, G. W. Synth.
Commun. 1993, 23, 1183–1187.

504
S. Kang et al. / Tetrahedron Letters 52 (2011) 502–504
6. Khan, F. N.; Jayakumar, R.; Pillai, C. N. J. Mol. Catal. A: Chem. 2003, 195, 139–145.
7. Okimoto, M.; Nagata, Y.; Sueda, S.; Takahashi, Y. Synth. Commun. 2003, 33,
3771–3776.
8. Yan, J.; Travis, B. R.; Borhan, B. J. Org. Chem. 2004, 69, 9299–9302.
9. Mu, R.; Liu, Z.; Yang, Z.; Liu, Z.; Wu, L.; Liu, Z.-L. Adv. Synth. Catal. 2005, 347,
1333–1336.
10. Khurana, J. M.; Sharma, P.; Gogia, A.; Kandpal, B. M. Org. Prep. Proced. Int. 2007,
39, 185–189.
MgSO4 and concentrated in vacuo. The residue was purified by flash column
chromatography to give 2. All the benzoic acid products were characterized by
1H and 13C NMR spectra, which are found to match with those reported
previously.23
20. To verify our proposed mechanism in Figure 1, we investigated the existence of
hydroperoxide, which is one of the strong experimental proofs. First, we tried
the oxidative cleavage of benzil 4a directly with sodium hydroperoxide or
hydrogen peroxide.24 Briefly, to a solution of benzil 4a (0.5 mmol) in THF
11. Asadolah, K.; Heravi, M. H.; Hekmatshoar, R.; Majedi, S. Molecules 2007, 12,
958–964.
12. Imanzadeh, G. H.; Zamanloo, M. R.; Mansoori, Y.; Khodayari, A. Chin. J. Chem.
2007, 25, 836–838.
13. Carrera, I.; Brovetto, M. C.; Ramos, J. C.; Seoane, G. A. Tetrahedron Lett. 2009, 50,
5399–5402.
14. (a) Ogata, Y.; Sawaki, Y.; Shiroyama, M. J. Org. Chem. 1977, 42, 4061–4066;
(b) Jones, D. D.; Johnson, D. C. J. Org. Chem. 1967, 32, 1402–1409; (c) Leffler, J. E.
J. Org. Chem. 1951, 16, 1785–1787.
15. Bhattacharjee, M.; Chettri, S. K.; Chaudhuri, M. K.; Islam, N. S.; Barman, S. R. J.
Mol. Catal. 1993, 78, 143–149.
16. Sato, K.; Aoki, M.; Noyori, R. Science 1998, 281, 1646–1647.
17. Joo, C.; Kang, S.; Kim, S. M.; Han, H.; Yang, J. W. Tetrahedron Lett. 2010, 51,
6006–6007.
18. Benzoins 1b, 1c, 1e–1g were prepared according to the procedure in Ref. 17.
Benzoin 1j was prepared according to the procedure in Ref. 21. They were
characterized by 1H NMR spectra, which are found to match with those
reported previously: 1b,22a 1c,17 1e,22b 1f,17 1g,17 and 1j.21 Benzoins 1a, 1d, and
1h were purchased from TCI and 1i was purchased from Aldrich.
19. General procedure for the oxidation of benzoins 1 to benzoic acids 2. To a solution
(7.5 mL) were added 30% H2O2 (51–204 lL, 0.5–2.0 mmol) followed by 0.2–
0.8 N NaOH or H2O (2.5 mL) at 0 °C. After stirring at room temperature, the
reaction mixture was quenched with 0.15 N aqueous Na2SO3 (10 mL), adjusted
to pH 1–2 with 0.1 N HCl, and extracted with CH2Cl2. The combined organic
layers were dried over MgSO4 and concentrated in vacuo. The residue was
purified by flash column chromatography to give 2a. A nearly quantitative
yield (99%) of benzoic acid 2a was obtained from benzil 4a within 1 h by using
2.0 equiv of H2O2 plus 2.0 equiv of NaOH. Interestingly, however, benzil 4a
remained nearly intact even after 26 h when treated with 2.0 (or 4.0) equiv of
H2O2 alone. We also tried the oxidative cleavage of benzils 4a and 4g using
NaH under O2 (1 atm).19 We observed that these benzils remained nearly intact
without forming benzoic acids 2a and 2g even after 20 h under such condition.
Altogether, hydroperoxide appears to be internally produced and acts as an
oxygen nucleophile for the NaH and O2-mediated oxidation of benzoins 1 to
benzoic acids 2 as proposed in Figure 1.
21. Stetter, H.; Rämsch, R. Y. Synthesis 1981, 477–478.
22. (a) Shimakawa, Y.; Morikawa, T.; Sakaguchi, S. Tetrahedron Lett. 2010, 51,
1786–1789; (b) Singh, P.; Mittal, A.; Kumar, S. Bioorg. Med. Chem. 2007, 15,
3990–3996.
23. (a) Shi, M.; Feng, Y.-S. J. Org. Chem. 2001, 66, 3235–3237; (b) Jiang, N.;
Ragauskas, A. J. J. Org. Chem. 2007, 72, 7030–7033; (c) Correa, A.; Martín, R. J.
Am. Chem. Soc. 2009, 131, 15974–15975; (d) Nair, V.; Varghese, V.; Paul, R. R.;
Jose, A.; Sinu, C. R.; Menon, R. S. Org. Lett. 2010, 12, 2653–2655; (e) Hanada, S.;
Yuasa, A.; Kuroiwa, H.; Motoyama, Y.; Nagashima, H. Eur. J. Org. Chem. 2010,
1021–1025.
of benzoins
1 (0.5 mmol) in distilled THF (5 mL) was added NaH (60%
dispersion in mineral oil, 1.0 mmol) at 0 °C. While stirring, the dark-blue
solution was allowed to warm to room temperature. After stirring under O2
(1 atm), until TLC analysis indicated complete consumption of the starting
material, the reaction mixture was quenched by adding 0.1 N HCl to a final pH
of 1–2 and extracted with CH2Cl2. The combined organic layers were dried over
24. Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron Lett. 1987, 28, 6141–6144.