Synthesis of cresotic acids by carboxylation of cresols with sodium ethyl carbonate

Article abstract of DOI:10.1134/S0965544116070161

Carboxylation of o-cresol, m-cresol, and p-cresol with sodium ethyl carbonate (SEC) proceeds regioselectively with the formation of cresotic acids: 2-hydroxy-3-methylbenzoic acid, 2-hydroxy-4-methylbenzoic acid, and 2-hydroxy-5-methylbenzoic acid, respectively. Optimal conditions for conducting the process have been found to be as follows: the reactants ratio of [cresol]: [sodium ethyl carbonate] = (1.5–2): 1, T = 180–185°C, P_CO2 = 10 atm, and t = 6–7 h. Simple and convenient methods for the synthesis of cresotic acids, which can be used for their industrial manufacturing, have been developed.

Full text of DOI:10.1134/S0965544116070161

ISSN 0965ꢀ5441, Petroleum Chemistry, 2016, Vol. 56, No. 7, pp. 646–650. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © Kh.A. Suerbaev, E.G. Chepaikin, N.Zh. Kudaibergenov, G.Zh. Zhaksylykova, 2016, published in Neftekhimiya, 2016, Vol. 56, No. 4, pp. 414–418.
Synthesis of Cresotic Acids by Carboxylation of Cresols
with Sodium Ethyl Carbonate
Kh. A. Suerbaeva, E. G. Chepaikinb, N. Zh. Kudaibergenova, and G. Zh. Zhaksylykovaa
a AlꢀFarabi Kazakh National University, Almaty, 050040 Republic of Kazakhstan
b Institute of Structural Macrokinetics and Materials Science, Russian Academy of Sciences, Chernogolovka, 142432 Russia
eꢀmail: khsuerbaev@mail.ru, echep@ism.ac.ru
Received May 12, 2015
Abstract—Carboxylation of oꢀcresol, mꢀcresol, and pꢀcresol with sodium ethyl carbonate (SEC) proceeds
regioselectively with the formation of cresotic acids: 2ꢀhydroxyꢀ3ꢀmethylbenzoic acid, 2ꢀhydroxyꢀ4ꢀmethylꢀ
benzoic acid, and 2ꢀhydroxyꢀ5ꢀmethylbenzoic acid, respectively. Optimal conditions for conducting the proꢀ
cess have been found to be as follows: the reactants ratio of [cresol] : [sodium ethyl carbonate] = (1.5–2) : 1,
T
= 180–185°C, PCO = 10 atm, and
t
= 6–7 h. Simple and convenient methods for the synthesis of cresotic
2
acids, which can be used for their industrial manufacturing, have been developed.
Keywords: cresotic acids;
oꢀcresol, mꢀcresol, pꢀcresol, carboxylation, carbon dioxide, sodium ethyl carbonate
DOI: 10.1134/S0965544116070161
Use of carbon dioxide as a source of carbon in nantly in the form of sodium and potassium phenoꢀ
organic synthesis is a challenging problem in current lates) was reported in a series of works by Japanese
organic and petroleum chemistry [1]. The great interꢀ researchers [6–8].
est stirred by this problem is manifested in the increasꢀ
ing rate of growth in the number of scientific publicaꢀ
tions devoted to this subject. It should be noted that
the utilization of carbon dioxide in chemical synthesis
is important for environmental protection as well,
since it is one of the ways for reducing the emission of
carbon dioxide, which is the main component of
greenhouse gases, into the atmosphere [1, 2]. One of
the most promising lines in the use carbon dioxide in
organic synthesis is the preparation of carboxylic acids
and their derivatives, organic compounds containing
the carboxyl С(О)–О– or/and the amide С(О)–NH2
group (carboxylic acids, esters, lactones, organic carꢀ
bonates and carbamates, ureas, amides, etc.) [1, 3].
Currently, supercritical CO2 is widely used as a
medium for conducting chemical reactions, including
its use as a reagent for the carboxylation of arenes [4].
Earlier, we conducted quite detailed studies of the
carboxylation reaction of hydroxyarenes (phenol and
naphthols) with readily available CO2 derivatives,
namely, alkali metal salts of alkyl carbonates, and
found that the reaction could be conducted without a
solvent [9–11]. Optimal conditions for conducting the
process were identified. The products of carboxylation
of cresols, methylꢀsubstituted phenolcarboxylic acids
(cresotic acids), find a widespread application as phoꢀ
tostabilizers, pharmaceuticals, and pesticides [12, 13].
Currently, the carboxylation of alkali metal cresylates
with carbon dioxide under pressure (Kolbe–Schmitt
reaction) is the main industrial method for the syntheꢀ
sis of cresotic acids. The method has a number of seriꢀ
ous disadvantages, the main of which is the need for
the preliminary synthesis of alkali metal cresylates.
The production of cresylates is complicated by the
laborꢀintensive technology of their preparation (water
removal by vacuum distillation) and high hygroscopicꢀ
ity of dry alkali metal cresylates [14–16].
The use of alkali metal salts of ethyl carbonate in
the phenol carboxylation reaction was first reported by
Jones [5]. Slow heating of a mixture of phenol with a
suspension of sodium ethyl carbonate (SEC) in ethaꢀ
nol to 175°C with the simultaneous removal of the solꢀ
vent and some unreacted phenol by distillation (under
reduced pressure) and the subsequent treatment of the
reaction mixture with water gave salicylic acid in a
yield of 50%. When using potassium ethyl carbonate,
The aim of this work was to develop an improved
method for the synthesis of cresotic acids via the carꢀ
boxylation of
mꢀcresol, pꢀcresol, and oꢀcresol with the
sodium salt of ethyl carbonate.
EXPERIMENTAL
The chemical used were dry sodium ethyl carbonꢀ
a mixture of salicylic and
pꢀhydroxybenzoic acids was
obtained. Later, the use of alkali metal salts of alkyl
carbonates as carboxylating agents in the carboxylaꢀ ate, synthesized by reacting carbon dioxide with
tion reaction of phenol and its derivatives (predomiꢀ sodium ethoxide as described in [8, 9], and metaꢀ,
646

SYNTHESIS OF CRESOTIC ACIDS BY CARBOXYLATION OF CRESOLS
647
paraꢀ, and orthoꢀcresols (SigmaꢀAldrich). The experꢀ ture was treated with water. The obtained aqueous
iments were conducted in the solventꢀfree mode in a solution was extracted with ether to separate unreꢀ
medium of gaseous СО2. The identity of synthesized acted
p
ꢀcresol. From the ether phase, 2.2 g of unreꢀ
acted
pꢀcresol was recovered. The product (2ꢀ
cresotic acids was determined by the melting point and
IR and NMR data. The IR spectra were recorded on a
Mattson SatelliteꢀFTIR Fourierꢀtransform IR specꢀ
trometer in the frequency range of 4000–400 cm–1 and
the NMR spectra were recorded on a Bruker DPX 400
instrument operating at a frequency of 300 MHz. Tetꢀ
ramethylsilane was used as the standard.
hydroxyꢀ5ꢀmethylbenzoic acid) was isolated by acidiꢀ
fying the aqueous phase with hydrochloric acid to
afford 2.67 g (88.0%) of 2ꢀhydroxyꢀ5ꢀmethylbenzoic
acid; the yield calculated on a
was 97.3%. m =149–150°C.
2ꢀHydroxyꢀ4ꢀmethylbenzoic acid (yield, 74.2%)
and 2ꢀhydroxyꢀ3ꢀmethylbenzoic acid (yield, 38%)
were also synthesized according to the above proceꢀ
pꢀcresol reacted basis
T
Preparation of 2ꢀHydroxyꢀ5ꢀMethylbenzoic Acid
dure by reacting sodium ethyl carbonate with mꢀcresol
A glass reactor placed into a steel autoclave and
equipped with a stirrer, electric heating, and carbon
dioxide gas inlet (outlet) fittings, was loaded with
and
o
ꢀcresol, respectively.
RESULTS AND DISCUSSION
4.33 g (0.04 mol) of
of sodium ethyl carbonate (reactants ratios was
ꢀcresol] : [sodium ethyl carbonate] = 2 : 1); the autoꢀ
clave was pressurized; purged twice with СО2 to
remove air; and filled with СО2 to a pressure of 10 atm;
after which stirring and heating were switched on. The
reaction mixture was heated to 185°C over 4 h (at a
heating rate of 40°C/h) and held at this temperature
and a СО2 pressure of 10 atm for 3 h. After that, stirꢀ
pꢀcresol and 2.24 g (0.02 mol)
There are no published data on the carboxylation of
ꢀcresol, ꢀcresol, or ꢀcresol with alkali metal salts of
alkyl carbonates. In this work, the carboxylation reacꢀ
tion of cresols with sodium ethyl carbonate was thorꢀ
[p
o
p
m
oughly studied using reagent grade
oꢀcresol, pꢀcresol,
and ꢀcresol (SigmaꢀAldrich) (Scheme 1). It was
m
found that sodium ethyl carbonate could be used for
the carboxylation of cresols. The influence of the reacꢀ
ring and heating were stopped and the autoclave was tion conditions on the course of the process and the
cooled down to room temperature. The reaction mixꢀ product yield was examined.
OH
H3C
COOH
38%
оꢀcresol
mꢀcresol
pꢀcresol
OH
COOH
74%
NaOEt
CO2
NaOC(O)OEt
H3C
OH
COOH
CH3
88%
Scheme 1. Carboxylation of cresols with sodium ethyl carbonate.
It was found that under the test conditions, the carꢀ dependence of the yield of the product (2ꢀhydroxyꢀ4ꢀ
methylbenzoic acid) on the reaction temperature is
nonmonotonic in character. With the increase in the
temperature from 120 to 180°C, the product yield
increases dramatically from 15.2 to 71.5%, but it drops
to 64.8% during the further increase in temperature to
190°C (Fig. 1).
boxylation of mꢀcresol with sodium ethyl carbonate
proceeded regioselectively at the ꢀposition relative
to the hydroxyl group with the exclusive formation of
2ꢀhydroxyꢀ4ꢀmethylbenzoic acid. The results of
studying the effect of the reaction conditions for the
o
carboxylation of mꢀcresol with sodium ethyl carbonate
The optimum values of the CO2 pressure and
the reaction time are 10 atm and 7 h, respectively
(Figs. 2, 3). Relatively cheap carbon dioxide is used
on the product yield are presented in Figs. 1–4. Since
the reaction is conducted without introducing a forꢀ
eign solvent, its role is played by mꢀcresol and, as the
reaction proceeds further, by the ethanol released. The as an inert gas. The optimum ratio of the reactants is
PETROLEUM CHEMISTRY Vol. 56
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648
SUERBAEV et al.
80
70
60
50
40
30
20
10
75
70
65
60
55
50
110 120 130 140 150 160 170 180 190 200
, °C
45
T
8
9
10
11
CO , atm
12
13
14
P
2
Fig. 1. Effect of temperature on the yield of
mꢀcresotic
acid (
α
).
m
ꢀCresol : SEC = 2,
P
= 10 atm, and
t
= 6 h.
CO2
Fig. 2. Effect of СО pressure on the yield of
m
ꢀcresotic
2
acid (α). mꢀCresol : SEC = 2, T = 180°C, and t = 6 h.
75
70
65
60
55
50
45
54
52
50
48
46
44
42
40
38
36
34
5
6
7
8
9
10
0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6
n
t, h
Fig. 3. Effect of the reaction time (
ꢀcresotic acid. ꢀCresol : SEC = 2,
= 10.
t
, h) on the yield of
Fig. 4. Yield of
molar ratio of
160°C, = 10 atm, and t
m
m
ꢀcresotic acid (
ꢀcresol to sodium ethyl carbonate (
= 6 h.
α
) depending on the initial
m
m
T
= 180°C, and
n). T =
P
P
CO2
CO2
[mꢀcresol] : [sodium ethyl carbonate] = 1.5 : 1 (Fig. 4). bon dioxide above the optimum value, the properties
It should be noted that an increase in the yield of saliꢀ of the medium change as a result of its high solubility
cylic acid during the carboxylation of phenol with (Fig. 2). Ethanol, which acts as a cosolvent, is released
sodium ethyl carbonate in the case of an excess during the reaction. It is likely that the maximum in
amount of the substrate (phenol) used was reported in the yield (Fig. 4) in the case of the increase in the
[9]. Under the optimum conditions found in this study cresol/SEC ratio is due to the shortage of ethanol for
for the ꢀcresol carboxylation reaction with sodium the creation of the optimum composition of the
mꢀ
m
ethyl carbonate, the yield of 2ꢀhydroxyꢀ4ꢀmethylbenꢀ medium.
zoic acid is 74.2% and the yield calculated on a reacted
It has been found that sodium ethyl carbonate can
be used as a carboxylating agent in the carboxylation
mꢀcresol basis is 91.0%.
The nonmonotonic pattern of curves in Figs. 1–4 reaction of
oꢀcresol and pꢀcresol. The carboxylation of
can be associated with the following. The decrease in ꢀcresol with sodium ethyl carbonate was
p
the yield with the increase in the temperature (Fig. 1) found to proceeded regioselectively with the formaꢀ
and the reaction time (Fig. 3) above optimum values tion of 2ꢀhydroxyꢀ5ꢀmethylbenzoic acid. The effect of
can be due to side reactions (decarboxylation and tar the reaction conditions on the product yield was invesꢀ
formation). It can be assumed that at a pressure of carꢀ tigated (Table 1). Under the optimum reaction condiꢀ
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SYNTHESIS OF CRESOTIC ACIDS BY CARBOXYLATION OF CRESOLS
pꢀcresol with sodium ethyl carbonate
649
Carboxylation of
Run
Reaction conditions
Yield of 2ꢀhydroxyꢀ5ꢀ
methylbenzoic acid,
wt %
Reactant ratio
[pꢀcresol] : [sodium
ethyl carbonate]
no.
T
, °C
PCO
,
atm
time, h
2
1
2
1 : 1
2 : 1
3 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
185
185
185
150
170
180
195
185
185
185
185
185
10
10
10
10
10
10
10
8
7
7
7
7
7
7
7
7
7
5
6
8
53.7
88.1
74.3
48.8
72.4
80.0
80.5
38.6
74.4
70.3
72.3
75.0
3
4
5
6
8
9
11
12
13
15
12
10
10
10
tions ([
p
ꢀcresol] : [sodium ethyl carbonate] = 2 : 1, hydroxyꢀ3ꢀmethylbenzoic acid, the protons of the
= 185°C, РCO = 10 atm, and t = 7 h), the yield of aromatic ring in the 4ꢀ and 6ꢀpositions appear as douꢀ
2
Т
blets at 7.36 and 7.78 ppm, respectively, and the proꢀ
ton in the 7ꢀposition, gives a triplet at 6.68 ppm. The
methyl group produces a singlet at 2.3 ppm. The carꢀ
boxyl and hydroxyl protons appear as a broadened sigꢀ
nal at 10.6 ppm because of a strong hydrogen bond.
2ꢀhydroxyꢀ5ꢀmethylbenzoic acid reached 88.1% and
the yield calculated on the reacted
97.3%.
pꢀcresol basis was
It was found that the oꢀcresol carboxylation reacꢀ
tion with sodium ethyl carbonate also proceeded
selectively with the exclusive formation of 2ꢀhydroxyꢀ
3ꢀmethylbenzoic acid. It should be noted that
In summary, it has been shown that sodium ethyl
carbonate can be used as a carboxylating agent in the
carboxylation reaction of cresols. It has been
in the case of
substantially lower yield of the product as compared
to ꢀcresol and ꢀcresol. In ꢀcresol carboxylation
under the optimum conditions found for the reaction
of ꢀcresol with sodium ethyl carbonate ([ ꢀcresol] :
[sodium ethyl carbonate] = 2 : 1, = 185°С, PСО
oꢀcresol, the reaction proceeds with a
found that the carboxylation of
oꢀcresol, mꢀcresol, or
p
ꢀcresol proceeds regioselectively with the formation
p
m
o
of 2ꢀhydroxyꢀ3ꢀmetheylbenzoic acid, 2ꢀhydroxyꢀ4ꢀ
metheylbenzoic acid, or 2ꢀhydroxyꢀ5ꢀmetheylbenꢀ
zoic acid, respectively. Optimum conditions for conꢀ
ducting this reaction have been found. The developed
simple and convenient methods for the synthesis of
cresotic acids can be used for their industrial manufacꢀ
turing.
p
o
Т
=
2
10 atm, = 7 h), the yield of the product (2ꢀhydroxyꢀ
3ꢀmethylbenzoic acid) is 38.0% and the yield calcuꢀ
lated on the reacted ꢀcresol basis is 90.1%.
The synthesized compounds were identified by
matching a physicochemical constant ( m), by the
t
o
T
REFERENCES
absence of melting point depression for a mixed samꢀ
ple of the products with authentic reagentꢀgrade samꢀ
ples of 2ꢀhydroxyꢀ3ꢀbenzoic acid, 2ꢀhydroxyꢀ4ꢀbenꢀ
zoic acid, and 2ꢀhydroxyꢀ5ꢀbenzoic acid, as well as by
the IR and NMR data. In the IR spectra of all the synꢀ
thesized compounds exhibit the band at 1620–
1660 cm–1 (carboxyl group) and a broad diffuse band
at 2300–3500 cm–1 (due to hydrogenꢀbonded
1. Carbon dioxide as a Source of Carbon: Biochemical and
Chemical Uses, Ed. by M. Aresta and G. Forti
(D. Reidel, Dordrecht, 1987).
2. Organic and Bioꢀorganic Chemistry of Carbon Dioxide
,
Ed. by S. Inoue and N. Yamazaki (Kodansha, Tokyo,
1982).
3. Kh. A. Suerbaev, Eur. Chem.ꢀTechnol. J. 12, 105
1
hydroxyl groups). In the H NMR spectrum of 2ꢀ
(2010).
PETROLEUM CHEMISTRY Vol. 56
No. 7
2016

650
SUERBAEV et al.
4. A. V. Shlyakhtin, S. Z. Vatsadze, D. P. Krut’ko, et al., 11. Kh. A. Suerbaev, E. G. Chepaikin, F. M. Kanapieva,
Sverkhkrit. Flyuidy: Teor. Prakt.
71, 21 (2012).
and G. Zh. Seitenova, Pet. Chem. 49, 265 (2009).
5. I. J. Jones, Chem. Ind., 1245 (1958).
6. I. Hirao, T. Kondo, and T. Kito, Kogyo Kagaku Zasshi
12. D. E. Hyams, A. N. Howard, I. E. Evans, and
H. H. Davison, Diabetologia 7, 94 (1971).
72, 692 (1969).
7. T. Kito, T. Kondo, H. Ago, et al., Kogyo Kagaku Zasshi
13. L. G. Shakirov, P. M. Zobov, and A. Z. Bikkulov, Zh.
Prikl. Khim. 58, 872 (1985).
73, 742 (1970).
14. A. S. Lindsey and M. Jeskey, Chem. Rev. 57, 583
(1957).
8. T. Kito and I. Hirao, Bull. Chem. Soc. Jpn. 44, 3123
(1971).
15. L. G. Shakirov, P. M. Zobov, and A. Z. Bikkulov, Zh.
Prikl. Khim. 58, 963 (1985).
9. Kh. A. Suerbaev, O. E. Mikhnenko, G. B. Akhmetova,
et al., Pet. Chem. 45, 41 (2005).
10. Kh. A. Suerbaev, O. E. Mikhnenko, G. B. Akhmetova,
16. V. N. Khlebnikov, L. G. Shakirov, O. E. Kuznetsov, and
A. Z. Bikkulov, Zh. Prikl. Khim. 62, 626 (1989).
et al., Pet. Chem. 45, 335 (2005).
Translated by E. Boltukhina
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