Efficient and rapid method for the oxidation of electron-rich aromatic aldehydes to carboxylic acids using improved basic hydrogen peroxide

Article abstract of DOI:10.1080/00397910500408456

An efficient and rapid method for oxidation of electron-rich aromatic aldehydes to their corresponding carboxylic acids in excellent yields was developed. It is based on the oxidation of methoxy-substituted benzaldehydes in methanol with an improved aqueous basic hydrogen peroxide system. Benzaldehydes with electronwithdrawing substituents are oxidized to the corresponding carboxylic acid in excellent yields under mild reaction conditions. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500408456

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Efficient and Rapid Method for the Oxidation
of Electron‐Rich Aromatic Aldehydes to
Carboxylic Acids Using Improved Basic
Hydrogen Peroxide
Zhi‐Qi Cong a , Chun‐Ian Wang b , Tie Chen a & Bing‐Zhu Yin a
a Department of Chemistry, College of Science, Yanbian University, Yanji,
China
b Department of Pharmacy and Applied Chemistry, Jilin Institute of Chemical
Technology, Jilin, China
Published online: 16 Aug 2006.
To cite this article: ZhiQi Cong , ChunIan Wang , Tie Chen & BingZhu Yin (2006) Efficient and Rapid Method
for the Oxidation of Electron‐Rich Aromatic Aldehydes to Carboxylic Acids Using Improved Basic Hydrogen
Peroxide, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 36:5, 679-683
To link to this article: http://dx.doi.org/10.1080/00397910500408456
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Synthetic Communicationsw, 36: 679–683, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500408456
Efficient and Rapid Method for the
Oxidation of Electron-Rich Aromatic
Aldehydes to Carboxylic Acids Using
Improved Basic Hydrogen Peroxide
Zhi-Qi Cong
Department of Chemistry, College of Science, Yanbian University,
Yanji, China
Chun-Ian Wang
Department of Pharmacy and Applied Chemistry, Jilin Institute
of Chemical Technology, Jilin, China
Tie Chen and Bing-Zhu Yin
Department of Chemistry, College of Science, Yanbian University,
Yanji, China
Abstract: An efficient and rapid method for oxidation of electron-rich aromatic
aldehydes to their corresponding carboxylic acids in excellent yields was developed.
It is based on the oxidation of methoxy-substituted benzaldehydes in methanol with
an improved aqueous basic hydrogen peroxide system. Benzaldehydes with electron-
withdrawing substituents are oxidized to the corresponding carboxylic acid in
excellent yields under mild reaction conditions.
Keywords: Basic hydrogen peroxide, electron-rich aromatic aldehydes, oxidation
Numerous methods have been described for the oxidation of aldehydes to their
corresponding carboxylic acid.[1,2] However, environmental considerations
Received in Japan September 1, 2005
Address correspondence to Bing-Zhu Yin, Department of Chemistry, College
of Science, Yanbian University, Yanji 133002, China. Tel.: 86-433-2732298;
Fax: þ86-433-2758088; E-mail: zqcong@ybu.ed.cn
679

680
Z.-Q. Cong et al.
have shifted the attention to Baeyer–Villiger type reaction.[3] The activation
of aqueous hydrogen peroxide has captivated researchers’ interest in the use of
this high-oxygen-content, relatively inexpensive, and environmentally
friendly oxidant for oxidation transformation in synthetic chemistry. Tremen-
dous efforts have been made to develop a novel catalyst system for the
oxidation of aromatic and aliphatic aldehyde, such as combinations of
hydrogen peroxide with sodium hypochlorite,[4] benzeneseleninic acid,[5]
selenium(IV) oxide,[6] methyltrioctyl-ammonium tetrakis (oxodiperoxotung-
sto) phosphate,[7] [CH3(n-C8H17)3N]HSO4,[8] Sn-Beta zeolites,[9] or formic
acid.[10] Recently, urea-hydrogen peroxide (UHP-H2O2) has been also used
for this purpose under acid[11] and basic conditions,[12] respectively.
But these reactions don’t prove to be satisfactory for oxidation of
electron-rich aromatic aldehydes to carboxylic acid. Generally speaking, the
electron density on the benzene ring largely determines Baeyer–Villiger
reaction to either acid or phenol. Electron-withdrawing substituents favor
hydrogen migration to yield acid, whereas electron-donating substituents
favor ring migration to yield phenol. To the best of our knowledge, the
oxidation of methoxy-substituent benzaldehyde using hydrogen peroxide
under neutral conditions gave few corresponding acids and more phenol.[13]
The selectivity oxidation of ortho formyl of cyclopaldic acid to the corre-
sponding carboxyl in 2N aqueous sodium hydroxide has been reported pre-
viously. However, hydrogen peroxide is invalid to another formyl of
cyclopaldic acid as well as cyclopolic acid under the same conditions.[14]
Recently, a number of articles[4–10] have reported the oxidation of aromatic
aldehydes having electron-withdrawing substituents to their corresponding
carboxylic acid in good yields with aqueous hydrogen peroxide. In
summary, the previous literature was limited on the oxidation of electron-
rich aromatic aldehydes to their corresponding carboxylic acid using
aqueous hydrogen peroxide under acidic, neutual, or alkaline conditions,
which usually gave phenol and formate. Herein we report the high-yield
oxidation of electron-rich benezaldehydes to their corresponding carboxylic
acids by an improved basic hydrogen peroxide system.
The oxidation of methoxy-substituted benzaldehydes is very easy and
proceeds within 20–30 min from addition of 30% H2O2 to the mixture of
aromatic aldehyde and 50% aqueous KOH (or 38% aqueous NaOH) in
methanol at reflux. (An aqueous 38% sodium hydroxide is also available to
the current scale reaction.) The optimum molar ratio substrate to KOH
and H2O2 was found to be 1 : 4 : 6(8). The concentration percent of KOH is
the key to efficient oxidation. We assumed that with an aromatic aldehyde,
addition of peroxide ion to the positive carbonyl carbon led to a like-hemiacetal
intermediate, then removal of a proton from the presumed intermediate would
occur at a faster rate in the presence of strong hydroxide ion than aryl group
migration. However, the lower concentration percent of H2O2 (e.g., 15%
H2O2) gave a less satisfactory result under the same basic conditions and
quite a few unchanged aldehydes were retrieved. The reaction temperature

Oxidation of Electron-Rich Aromatic Aldehydes
681
Scheme 1.
may be the other important factor for the oxidation of aldehydes with electron-
donating substituents to the corresponding carboxylic acid. A mixture of
the corresponding phenolic product, acid product, and most unchanged
aldehydes was afforded at room temperature (Scheme 1).
Examples of the simple oxidation are shown in Table 1. The yields using
our basic hydrogen peroxide system varied from excellent (3-methoxybenz-
aldehyde to 3-methoxy benzoic acid, 97%) to good (2,3-dimethoxy benz-
aldehyde to 2,3-dimethoxybenzoic acid, 93%; 2,3,4-trimethoxy benzaldehyde
to 2,3,4-trimethoxybenzoic acid, 81%). Apparently, the effect of ring substitu-
ents for the oxidative transformation of aldehydes varied with numbers of
methoxyl. Steric effects also seem to affect the oxidation of benzaldehyde
Table 1. Oxidation of aromatic aldehydes to their carboxylic acida
Carboxylic acid
Substituted
benzaldehyde
(6 mmol)
H2O2
Base
Timeb Yield
(mmol) (mmol) (min) (%)c
mp,d 8C (lit.)e
Benzaldehyde
24
24
24
30
36
36
42
18
18
18
24
24
24
24
15
15
15
20
20
20
20
87
83
92
98
95
97
93
121–123 (121–123)
239–244 (239–245)
240–244 (239–245)
177–180 (179–182)
97–99 (98–100)
4-Nitrobenzaldehyde
4-Nitrobenzaldehydef
4-Methylbenzaldehyde
2-Methoxybenzaldehyde
3-Methoxybenzaldehyde
2,3-Dimethoxybenz-
aldehyde
105–108 (106–108)
118–121 (122–124)
2,5-Dimethoxybenz-
aldehyde
42
48
48
24
24
24
20
30
30
87
81
82
75–77 (76–78)
97–99 (99–102)
141–144 (143–145)
2,3,4-Trimethoxybenz-
aldehyde
2,4,5-Trimethoxybenz-
aldehyde
aExperiments run at reflux unless otherwise stated.
bThe total time including dropwise and reflux.
cThe yields are for isolated products.
dCrude product, uncorrected, measured on a Bu¨chi apparatus.
eTaken from the Aldrich Chemical Co. catalogue unless otherwise stated.
fThe experiment runs at room temperature.

682
Z.-Q. Cong et al.
derivatives. The oxidation of 2-methoxybenzaldehyde gave 2-methoxyben-
zoic acid in 95% yield and 3-methoxybenzaldehyde in 97% yield. The same
results happened to dimethoxy-substituted and trimethoxy-substituted benz-
aldehydes. Similarly, the oxidation of 3-methoxybenzaldehyde using the
system UHP–NaOH gave 3-methoxybenzoic acid in 95% yield. The
oxidation of 3,4-dimethoxybenzaldehyde gave the corresponding benzoic
acid in only 63% yield, and the oxidation of trimethoxy-substituted
benzaldehydes weren’t reported.[12]
In addition, the oxidations of benzaldehyde, 4-methylbenzaldehyde, and
4-nitrobenzaldehyde under identical conditions were also investigated.
Similar to methoxy-substituted benezaldehyde, the oxidation of 4-methylben-
zaldehyde gave 4-methyl benzoic acid in 98% yield. However, the oxidations
of benzaldehyde and 4-nitrobenzaldehyde under identical conditions gave the
corresponding benzoic acid in 87% and 83% yields, respectively. It is
important to note that the reaction of 4-nitrobenzaldehyde proceeded at
room temperature in excellent yield (92%).
In conclusion, the oxidation of aromatic aldehydes with electron-
withdrawing as well as electron-donating substituents to their carboxylic
acid using an improved basic hydrogen peroxide system represents an
efficient, rapid, practical procedure, particularly in the case of electron-rich
benzaldehydes. The methodology requires relatively safe and commercially
available reagents and proved to be especially useful in cases where the
product, carboxylic acid, is insoluable.
EXPERIMENTAL
Materials
All of the aldehydes were purchased from Aldrich Chemical Company (USA).
Hydrogen peroxide (30%) used was commercial analytical grade and wasn’t
standardized. The melting points were determined by using a Bu¨chi
apparatus and are uncorrected.
Typical Procedure
Aqueous hydrogen peroxide (30%, 4.8 mL, 48 mmol) was added dropwise to a
stirred solution of 50% aq. KOH (1.76 mL, 24 mmol) and 2,4,5-trimethoxy
benzaldehyde (1176 mg, 6 mmol) in methanol (10 mL) at 658C for 20 min.
The mixture was then stirred at the same temperature for 10 min, cooled,
acidified with concentrated hydrochloride to give 2,4,5-trimethoxy benzoic
acid (1042 mg, 82%). Mp 141–1448C (crude product), lit. 143–1458C (the
Aldrich Chemical Co. catalogue).

Oxidation of Electron-Rich Aromatic Aldehydes
ACKNOWLEDGMENT
683
The authors are grateful to the National Science Foundation of China for the
financial support (No. 20462001).
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