COMMUNICATION
Theoretical study of Al(III)-catalyzed conversion of glyoxal to glycolic
acid: dual activated 1,2-hydride shift mechanism by protonated Al(OH)3
speciesw
Takashi Ohshima,*a Yoshihiro Yamamoto,*b Usaji Takaki,b Yoshihisa Inoue,b Takuya Saeki,b
Kenji Itou,b Yusuke Maegawa,a Takanori Iwasakia and Kazushi Mashima*a
Received (in Cambridge, UK) 10th February 2009, Accepted 3rd March 2009
First published as an Advance Article on the web 26th March 2009
DOI: 10.1039/b902729g
Density functional theory calculations demonstrate that
Al(III)-catalyzed conversion of glyoxal to glycolic acid proceeds
via a 7-membered dual Lewis acid-hydrogen bonding activa-
tion transition state of the 1,2-hydride shift, rather than the
previously proposed 5-membered metal-alkoxide chelate activation
transition state.
excellent precedent of the Lewis acid (as opposed to Brønsted
base)-assisted Cannizzaro reaction of aryl glyoxal,6 we
examined various Lewis acids as a catalyst. Al, Si, Ga, and
Sn complexes were good catalysts for this reaction, whereas B,
Mn, and Fe complexes gave only moderate yields. Among
them, AlX3 complexes had higher catalyst activity than the
other complexes. Because glycolic acid (1) is highly soluble in
water and cannot be distilled even under high vacuum, it is
difficult to remove counter anions (Xꢀ), such as chloride,
nitrate, and sulfate, from the aqueous solution of product 1.
Thus, Al(OH)3 was selected as the best catalyst for this
process. In the presence of 0.2 mol% of Al(OH)3, the
reaction completed within 3 h at 165 1C to afford 1 in 92%
yield (entry 3).5 This catalysis has several advantages: simple
procedures, mild conditions, and inexpensive and harmless
reagents. In addition, large-scale reaction (10 mol scale)
proceeded with the same efficiency.
Glycolic acid (1) is one of the smallest molecules with both
carboxylic acid and alcohol functionalities. Due to the
hydroxyl group at the a-position of the carboxylic acid, 1
has higher acidity (pKa 3.83) and stronger chelating properties
toward metal ions than an unfunctionalized carboxylic acid
(pKa E 4.8). Thus, 1 is used industrially for rust removal,
degreasing, etc. Although 1 occurs naturally in sugarcane,
sugar beets, and in several fruits as a trace component, a
highly efficient manufacturing process is required to provide a
constant supply of this mass product. The acid-catalyzed
reaction of formaldehyde with water under carbon monoxide
produces an aqueous solution of 1 on an industrial scale,1 but
this process requires high temperature (200 1C), high pressure
(4300 kg cmꢀ2), and removal of the remaining formaldehyde
from the product mixture. On a laboratory scale, 1 can be
synthesized by (i) hydrolysis of monochloroacetic acid with
aqueous sodium hydroxide (42 equiv.)2 or (ii) a Cannizzaro-
type reaction of glyoxal (2) with aqueous sodium hydroxide
(41 equiv.).3 The use of more than stoichiometric amounts
of alkali metal hydroxide followed by acid treatment for
neutralization is not suitable, however, for large-scale production.
We developed a direct conversion of 2 to 1 that resulted in
high yield and high purity.4,5 We first found that 1 was
produced by simply heating a 15% aqueous solution of 2 in
a stainless autoclave (Table 1, entry 1). The yield of 1,
however, remained only moderate (up to 65%), even after
various attempts, leading to screening for acid catalysts.
Although some Brønsted acids, such as 1, showed a positive
effect, the yield was still unsatisfactory (entry 2). Based on the
Under strongly basic conditions, an internal Cannizzaro
reaction of 2 produces metal glycolate.3 The reaction condi-
tions of the current acid catalysis, however, are quite different
from the Cannizzaro conditions. Although a 1,2-hydride shift
mechanism was proposed in previous reports of the Lewis
acid-catalyzed Cannizzaro reaction,6a–c such a mechanism was
only speculative and has not been confirmed. To gain more
detailed information about the reaction mechanism of this
acid catalysis and to elucidate the effects of Brønsted and
Lewis acids, we performed theoretical studies using the
B3LYP7 hybrid density functional theory (DFT). Here we
provide an evaluation of two possible mechanisms, the
dehydration mechanism and the 1,2-hydride shift mechanism,
of this transformation. On the basis of the DFT calculations,
we propose that (i) the direct conversion of glyoxal (2) to
Table 1 Representative results of direct catalytic conversion of 2 to 1a
a Department of Chemistry, Graduate School of Engineering Science,
Osaka University, Toyonaka, Osaka 560-8531, Japan.
E-mail: ohshima@chem.es.osaka-u.ac.jp,
mashima@chem.es.osaka-u.ac.jp; Fax: +81-6-6850-6249;
Tel: +81-6-6850-6246
Entry
Catalyst
Yieldb (%)
b Catalyst Science Laboratory, Mitsui Chemicals, Inc.,
580-32 Nagaura, Sodegaura-city, Chiba 299-0265, Japan.
E-mail: Yoshihiro.Yamamoto@mitsui-chem.co.jp;
Fax: +81-438-64-2382; Tel: +81-438-64-2300
1
2
3
—
HOOCCH2OH (1) (10 mol%)
Al(OH)3 (0.2 mol%)
65
68
92
a
15% Aqueous solution of glyoxal (2, 646 mmol) in 500 mL stainless
b
w Electronic supplementary information (ESI) available: Experimental
and computational data. See DOI: 10.1039/b902729g
autoclave was heated at 165 1C. Determined by HPLC analysis.
ꢁc
This journal is The Royal Society of Chemistry 2009
2688 | Chem. Commun., 2009, 2688–2690