Acid-catalyzed hydrothermal formation of carbon-carbon bond in glycolic acid from a series of formaldehyde producers

Article abstract of DOI:10.1246/cl.2004.624

The acid-catalyzed hydrothermal reaction is reported which forms a new carbon-carbon bond in the hydroxy carboxylic acid. It is found that glycolic acid is produced from formaldehyde in hot water at 225°C with HCl. This reaction is a chemical evolution process from a C1 compound to a C2, and does not proceed in the absence of acid. A reaction of 0.3 M (mol/dm³) of formaldehyde with the double amount of HCl yielded 60% of the maximum possible amount.

Full text of DOI:10.1246/cl.2004.624

624
Chemistry Letters Vol.33, No.5 (2004)
Acid-Catalyzed Hydrothermal Formation of Carbon–Carbon Bond in Glycolic Acid
from a Series of Formaldehyde Producers
Saiko Morooka, Chihiro Wakai, Nobuyuki Matubayasi, and Masaru Nakaharaꢀ
Institute for Chemical Research, Kyoto University, Uji, Kyoto, 611-0011
(Received February 23, 2004; CL-040195)
The acid-catalyzed hydrothermal reaction is reported which
s-trioxane, formalin, or paraformaldehyde, it was sealed in a
quartz NMR tube with aqueous HCl solution at the condition
shown in Table 1. All s-trioxane, formalin, and paraformalde-
hyde produce formaldehyde, and their concentrations were ad-
justed to provide 0.3 M of formaldehyde at the reaction temper-
ature. The concentration of HCl was mostly set to 0.6 M so that it
matches with the condition achieved in the reaction of CH2Cl2;
one CH2Cl2 molecule generates two HCl molecules upon hy-
drolysis.4 The effects of HCl and of formic acid concentration
on the glycolic acid formation were examined by changing the
HCl concentration and by adding formic acid, respectively.
Each sample tube was heated in a furnace kept at the reac-
tion temperature of 225 ꢂ 1 ꢁC. After 2 h of reaction, the sample
was removed from the furnace and cooled down to room temper-
ature by air within a minute. After the reaction, the sample was
put in a Pyrex NMR tube (5.0-mm o.d.) and the 1H NMR spec-
trum was measured with ECA400 (JEOL).
To examine the necessity of HCl in glycolic acid formation,
reactions of 0.1 M s-trioxane with and without 0.6 M HCl were
studied. The product concentrations are shown in Figure 1. In
both experiments, methanol and formic acid formed, which re-
sults from two formaldehyde disproportionations.7 One is the
self-disproportionation between two formaldehydes, which gen-
erates methanol and formic acid, and the other is the cross-dis-
proportionation between formaldehyde and formic acid, which
generates methanol and CO2. It is striking that these reactions
proceed even under acidic condition in hot water, whereas the
classical Cannizzaro (disproportionation) reaction needs a large
amount of base catalyst at ambient condition.8 The formation of
glycolic acid was confirmed in the experiment with HCl, while
no glycolic acid was detected in the absence of HCl. Also, the
yield of glycolic acid was found to be reduced by ꢃ60% upon
the change in the HCl concentration from 0.6 to 0.3 M. Thus,
it is revealed that glycolic acid forms from formaldehyde in
two steps; the self-disproportionation of formaldehyde and the
acid-catalyzed reaction of formaldehyde and formic acid9 ex-
pressed as:
forms a new carbon–carbon bond in the hydroxy carboxylic acid.
It is found that glycolic acid is produced from formaldehyde in
hot water at 225 ꢁC with HCl. This reaction is a chemical evolu-
tion process from a C1 compound to a C2, and does not proceed
in the absence of acid. A reaction of 0.3 M (mol/dm3) of form-
aldehyde with the double amount of HCl yielded 60% of the
maximum possible amount.
Hot water dissolves a variety of organic substances, and can
be used as a clean alternative to harmful organic solvents. To de-
velop green chemistry using hot water, a systematic study of re-
actions in hot water is indispensable. In particular, synthetic re-
actions that form new bonds such as carbon–carbon or carbon–
oxygen bond are of surpassing interest.1–5 Conventionally, the
carbon–carbon bond formation is carried out under severe and
delicate conditions,6 typically in the presence of metal catalysts
or in use of a donor–acceptor pair (Diels–Alder). In stark con-
trast to these synthetic methods, it was demonstrated in a previ-
ous paper that a carbon–carbon bond is formed spontaneously in
glycolic acid from CH2Cl2 in hydrothermal condition without
any added catalysts.4 Still, the mechanism of this operationally
simple reaction needs to be disclosed; the glycolic acid produc-
tion is assumed to be originated in methanediol (hydrated form
of formaldehyde) formation and be catalyzed by HCl which is
generated in the course of the CH2Cl2 reaction. It is therefore
crucial to identify the key reaction step and characterize its be-
havior. In the present work, we investigate each hydrothermal
reaction step of formaldehyde. The reaction is examined sepa-
rately by changing the input reactant and acidity. We show that
the carbon–carbon bond formation in glycolic acid proceeds in
the presence of an acid catalyst. The process is a chemical evo-
lution process from a C1 compound to a C2 in hot water.
The reaction conditions are listed in Table 1. 1,3,5-Trioxane
(a trimer of formaldehyde, called s-trioxane hereafter), HCl
(2 M), and formic acid (99%) employed as the starting materials
were obtained from Nacalai and used without further purifica-
tion. CH2Cl2 was also purchased from Nacalai and was washed
with distilled water to remove methanol contained as polymer-
ization inhibitor. Paraformaldehyde (>95%) and 13C-enriched
formalin (20%) were obtained from Merck and ISOTEC, respec-
tively, and were used as received.
2 HCHO þ H2O ! CH3OH þ HCOOH
HCHO þ HCOOH ! HOCH2COOH:
ð1Þ
ð2Þ
From the synthetic point of view, it is of great interest to
control the reaction path weight among the self-disproportiona-
tion (S), the cross-disproportionation between formaldehyde and
formic acid (C), and the glycolic acid formation (G). The rates of
these three reactions can be described respectively as:
When CH2Cl2 is the starting material, it was sealed with wa-
ter in a quartz NMR tube of 2.2-mm i.d. and 3.0-mm o.d. The
concentration was set to 0.3 M when the reaction mixture be-
comes homogeneous. The filling factor of the sample (volume
ratio of the solution to the total sample tube) was set to 85%
at room temperature in order to make the gas phase volume neg-
ligible at the reaction temperature. When the starting material is
S rate / [HCHO]2
ð3Þ
ð4Þ
ð5Þ
C rate / [HCHO][HCOOH]
G rate / [HCHO][HCOOH][HCl]:
In the aim of the glycolic acid production, the self- and cross-dis-
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.5 (2004)
625
Table 1. The reaction conditions and the concentrations of the reac-
tants
500
400
s-Trixoane 0.1 M,
HCl 0.6 M
s-Trixoane 0.1 M,
HCl 0.6 M,
HCOOH 3.0 M
Dichloromethane 0.3 M
s-Trioxane 0.1 M
s-Trioxane 0.1 M,
HCl 0.3 M
Formaldehyde
Generator
Aldehyde
/mM
HCl
/mM
HCOOHa
Added/mM
Filling
Factor/%
dichloromethane
s-trioxane
s-trioxane
s-trioxane
s-trioxane
300
100
100
100
100
300
300
0
0
0
0
.0
85
71
71
71
50
71
71
300
250
300
600
600
600
600
0
3000
0
200
150
100
50
formalin
paraformaldehydeb
0
aThe hydrothermal decompositions of formic acid into CO or CO2 were
shown to occur in the present experimental condition.10
bParaformaldehyde is in the powder form when the sample is pre-
pared, because it requires long time to dissolve into water at room
temperature.
proportionations, which produce methanol, need to be sup-
pressed. When s-trioxane is treated under acidic hydrothermal
conditions, the glycolic acid formation does not proceed appre-
ciably until enough amount of formic acid is accumulated by
Eq 1. Also, in the beginning of the reaction, the self-dispropor-
tionation is dominant over the glycolic acid formation due to
high formaldehyde concentration; cf. the difference in the reac-
tion order in Eqs 3 and 5. We can increase the rate and the yield
of the glycolic acid formation by increasing [HCOOH] in Eq 5.
As seen in Eq 4, in fact, the addition of formic acid also accel-
erates the cross-disproportionation, which generates methanol.
According to Eq 5, on the other hand, the addition of HCl indu-
ces the glycolic acid formation only. Therefore, only when the
reaction mixture is acidic enough, the reaction rate of the glycol-
ic acid formation becomes larger than that of either self- or
cross-disproportionations, and the addition of formic acid effi-
ciently accelerates the glycolic acid formation.
To substantiate the effect of added formic acid, 0.1 M s-tri-
oxane and 0.6 M HCl were reacted with and without 3.0 M for-
mic acid, and the results were compared. When formic acid was
present in excess, the yield of glycolic acid was ꢃ4 times larger
than in the experiment without added formic acid. Figure 1 clear-
ly shows our success in the selective formation of glycolic acid
and the suppression of the disproportionation pathways. It is of
great importance to control the reaction pathway by simply mod-
ifying reactant concentrations.
Other than s-trioxane, formalin and paraformaldehyde were
treated with HCl in the same condition as s-trioxane, and they
reacted similarly. Not only the product species were in accord
but also their yields including glycolic acid agreed well. The dif-
ference in their yields of glycolic acid was within 10%. It is
therefore clarified that the glycolic acid formation does proceed
regardless of the initial form of formaldehyde.
According to the former study of glycolic acid formation
from CH2Cl2,4 the mechanism of the formation was considered
to consist of the following three steps; the formation of formal-
dehyde and HCl by the hydration of CH2Cl2, the formaldehyde
disproportionations, and the acid-catalyzed glycolic acid forma-
tion from formaldehyde and formic acid. In this reaction scheme,
HCl, which is a product in the first step, works as a catalyst. This
mechanism was not conclusively demonstrated in the previous
work. The present work verifies that glycolic acid does form
when the reaction is initiated with formaldehyde and HCl, and
does not in the absence of HCl.
0
Glycolic acid CH3OH
HCOOH CH2(OH)2
CH3Cl
Figure 1. The product concentrations in various reaction conditions.
The ordinate scale is changed at 250 mM. The arrows represent the ef-
fect of added formic acid on the product yields.
In the present work, an acidic hydrothermal reaction in
which glycolic acid, a C2 compound, forms from formaldehyde,
a C1 compound, is reported. The carbon–carbon bond formation
in this reaction proceeds without any metal catalysts and the re-
action condition is much milder than that in the conventional
scheme. The selective formation of glycolic acid was achieved
by the addition of formic acid under acidic hydrothermal condi-
tion. Besides the glycolic acid formation, the present work sug-
gests a new way of producing amino acids; the amination of hy-
droxyl group in glycolic acid leads to the formation of glycine,
the simplest amino acid.
This work is supported by the Grant-in-Aid for Scientific
Research (Nos. 14540531, 15205004, and 15076205) and the
Grant-in-Aid for Creative Scientific Research (No. 13NP0201)
from the Japan Society for the Promotion of Science and the
Ministry of Education, Culture, Sports, Science and Technology.
References and Notes
1
2
3
4
Y. Yamasaki, H. Enomoto, N. Yamasaki, and M. Nakahara, Bull. Chem.
Soc. Jpn., 73, 2687 (2000).
Y. Tsujino, C. Wakai, N. Matubayasi, and M. Nakahara, Chem. Lett.,
1999, 287.
Y. Nagai, C. Wakai, N. Matubayasi, and M. Nakahara, Chem. Lett., 32,
310 (2003).
C. Wakai, S. Morooka, N. Matubayasi, and M. Nakahara, Chem. Lett.,
33, 302 (2004).
Z. Zhang, Y. Dong, and G. Wang, Chem. Lett., 32, 966 (2003).
T. Banno, Y. Hayakawa, and M. Umeno, J. Organomet. Chem., 653, 288
(2002).
Y. Nagai, N. Matubayasi, and M. Nakahara, Chem. Lett., submitted.
J. March, ‘‘Advanced Organic Chemistry,’’ 4th ed., John Wiley & Sons,
New York (1992).
In the time evolution of the product concentrations shown in Ref. 4, the
decrease of formic acid corresponds well to the generation of glycolic
acid, which indicates the direct consumption of formic acid. According
to Refs. 4 and 10, furthermore, the pyrolysis of formic acid is a minor
reaction, which again indicates that the glycolic acid formation does
not proceed with CO; [CO] is too small compared to that required in
U. S. Patent 2152852 (1939).
5
6
7
8
9
10 C. Wakai, K. Yoshida, Y. Tsujino, N. Matubayasi, and M. Nakahara,
Chem. Lett., 33 (2004), in press.
Published on the web (Advance View) April 24, 2004; DOI 10.1246/cl.2004.624