Carboxylation of o-, m-, and p-chlorophenols with sodium ethyl carbonate

Article abstract of DOI:10.1134/S0965544117050103

The possibility for the synthesis of 5-chloro-2-hydroxybenzoic, 4-chloro-2-hydroxybenzoic, and 3-chloro-2-hydroxybenzoic acids via regioselective carboxylation of p-, m-, and o-chlorophenols, respectively, with sodium ethyl carbonate has been demonstrated

Full text of DOI:10.1134/S0965544117050103

ISSN 0965-5441, Petroleum Chemistry, 2017, Vol. 57, No. 5, pp. 436–440. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © Kh.A. Suerbaev, E.G. Chepaikin, N.Zh. Kudaibergenov, 2017, published in Neftekhimiya, 2017, Vol. 57, No. 3, pp. 325–328.
Carboxylation of o-, m-, and p-Chlorophenols
with Sodium Ethyl Carbonate
a,
b,
a
Kh. A. Suerbaev *, E. G. Chepaikin **, and N. Zh. Kudaibergenov
a
Al-Farabi Kazakh National University, Almaty, Kazakhstan
b
Institute of Structural Macrokinetics and Materials Science, Russian Academy of Sciences, Chernogolovka, Russia
e-mail: khsuerbaev@mail.ru
*
*
*e-mail: echep@ism.ac.ru
Received August 10, 2016
Abstract⎯ The possibility for the synthesis of 5-chloro-2-hydroxybenzoic, 4-chloro-2-hydroxybenzoic, and
3
-chloro-2-hydroxybenzoic acids via regioselective carboxylation of p-, m-, and o-chlorophenols, respec-
tively, with sodium ethyl carbonate has been demonstrated. Simple and convenient procedures developed in
this study for the synthesis of chlorohydroxybenzoic acids can be used for their preparative and industrial syn-
thesis.
Keywords: chlorophenolcarboxylic acids, chlorophenols, sodium ethyl carbonate, carboxylation
DOI: 10.1134/S0965544117050103
The problem of using carbon dioxide as a carbon reported in [7, 8]. It should be noted that alkali metal
source in chemical syntheses, which is also of great phenolates in the cited studies were mainly tested as
importance from the viewpoint of environmental pro- substrates in the reaction of carboxylation with alkali
tection because it is one of the ways to decrease the salts of alkylcarbonic acids, and the reaction was car-
concentration of carbon dioxide in the atmosphere, is ried out in various solvents. Earlier, we studied the
being widely discussed at present. Thus, the develop- carboxylation of phenol and naphthols and their
ment of effective methods for the preparation of useful derivatives with sodium and potassium alkyl carbon-
organic compounds from carbon dioxide is a highly ates. It was shown that these compounds can be suc-
demanding task [1, 2].
cessfully used for the direct carboxylation of phenols
(
naphthols) without their preliminary conversion into
Carboxylation of chlorophenolates of alkali metals
with carbon dioxide under pressure (Kolbe–Schmitt
reaction) is the main industrial method for the prepa-
ration of chlorophenolcarboxylic acids. The method
phenolates (naphtholates) and in the absence of sol-
vents [6, 9, 10].
In this work, we studied the carboxylation reaction
has a number of significant disadvantages, the main of of p-, m-, and o-chlorophenols with sodium ethyl car-
which is the need for the preliminary technologically bonate in order to develop a more advanced technique
labor-intensive synthesis of alkali metal chloropheno- for the synthesis of 5-chloro-2-hydroxybenzoic, 4-
lates because of the technological labor intensity of the chloro-2-hydroxybenzoic, and 3-chloro-2-hydroxy-
preparation of the latter (removal of water by vacuum benzoic acids. The chlorophenol carboxylation prod-
distillation) and their high hygroscopicity [3, 4].
ucts chlorophenolcarboxylic acids are valuable inter-
Carbon dioxide is quite inert, and the majority of mediates for the preparation of herbicides, medicinal
reactions involving it proceed only under certain con- drugs, and dyes because of their reactive substituent
ditions (the use of catalysts, severe process conditions, (chlorine) [3, 4, 11–13].
etc.). At the same time, many of the simplest deriva-
tives of carbon dioxide are reactive compounds. In
EXPERIMENTAL
particular, syntheses on the basis of alkali salts of
alkylcarbonic acids, which are readily synthesized
Dry sodium ethyl carbonate synthesized via the
from carbon dioxide and alcoholates of alkali metals, interaction of carbon dioxide with sodium ethoxide
are of interest [5]. It looks promising to use supercrit- and o-, m-, and p-chlorophenols (Sigma-Aldrich)
ical carbon dioxide as a medium for conducting the were used as the reagents. The experiments were car-
carboxylation reactions of organic compounds [6].
ried out without using solvents in the medium of gas-
The possibility of using alkali salts of alkylcarbonic eous carbon dioxide. The synthesis products
acids as a carboxylating agent for hydroxyarenes was were identified by physicochemical constants (T ),
m
436

CARBOXYLATION OF o-, m-, AND p-CHLOROPHENOLS
437
(no that, stirring and heating were stopped and the auto-
examination
of
mixed samples
melting point depression) with pure commercial clave was cooled to room temperature. The reaction
samples of 5-chloro-2-hydroxybenzoic, 4-chloro-2- mixture was treated with water; the resulting aqueous
hydroxybenzoic, and 3-chloro-2-hydroxybenzoic solution was extracted with toluene to separate unre-
1
acids, and IR and H NMR data. The IR spectra were acted p-chlorophenol. 5-Chloro-2-hydroxybenzoic
recorded on a Nicolet 5700 single-beam infrared spec- acid was isolated by acidifying the aqueous phase with
trometer (Thermo Electron Corporation, United hydrochloric acid. The product so obtained had a yield
–1
1
of 86.1% (1.49 g) and T = 172–173°C.
m
States) in the region of 400–4000 cm . The H NMR
spectra were recorded on a Brucker DPX 400 instru-
ment operating at a frequency of 300 MHz (reference
standard was tetramethylsilane).
4
-Chloro-2-hydroxybenzoic acid (T = 211–
m
2
13°C; yield, 76.2%) and 3-chloro-2-hydroxybenzoic
acid (T = 182–183°C; yield, 68.2%) were also syn-
m
thesized according to the above procedure by reacting
sodium ethyl carbonate with m-chlorophenol and o-
chlorophenol, respectively. The products (chlorophe-
nolcarboxylic acids) were identified by their physico-
Synthesis of 5-Chloro-2-Hydroxybenzoic Acid
A 2.57-g portion (0.02 mol) of p-chlorophenol and
1
.12 g (0.01 mol) of sodium ethyl carbonate (reactants
chemical constant (Т ), examination of samples in
m
ratio of [p-chlorophenol] : [sodium ethyl carbonate] =
mixture (no melting point depression) with pure com-
mercial samples of authentic chlorophenolcarboxylic
2
: 1) were charged into a glass insert placed into a steel
autoclave equipped with a stirrer, electric heating, and
an inlet (outlet) tube for gaseous carbon dioxide; the
autoclave was pressurized, purged twice to remove air,
and then filled with carbon dioxide to a pressure of
1
acids, and the IR and H NMR spectroscopy data.
RESULTS AND DISCUSSION
1
0 atm, after which stirring and heating were switched
on. The temperature of the reaction mixture was ele-
In this work, the solvent-free carboxylation reac-
vated to 190°C within 4 h (at a heating rate of tion of o-, m-, and p-chlorophenols with sodium ethyl
4
2.5°C/h) and the reaction mixture was held at this carbonate was studied in detail for the first time
temperature and a СО pressure of 10 atm for 2 h. After (Scheme).
2
OH
OH
COOH
COOH
−
HCl
Cl
о-chlorophenol Cl
COONa
COONa
−NaCl
OH
OH
NaOEt
m-chlorophenol
p-chlorophenol
CO2
NaOC(O)OEt
−HCl
−EtOH
Cl
−NaCl
Cl
OH
OH
COOH
COONa
−HCl
−NaCl
Cl
Cl
Scheme. The synthesis of chlorohydroxybenzoic acids via the carboxylation of chlorophenols.
It was found that sodium ethyl carbonate can be conditions, the carboxylation of o-, m-, and p-chloro-
successfully used for the carboxylation of chlorophe- phenols with sodium ethyl carbonate proceeds regi-
nols. The effect of various process conditions on the oselectively to form 3-chloro-2-hydroxybenzoic, 4-
behavior of the reaction and the product yield was chloro-2-hydroxybenzoic, and 5-chloro-2-hydroxy-
studied. It was found that under the given reaction benzoic acids, respectively.
PETROLEUM CHEMISTRY Vol. 57 No. 5 2017

4
38
SUERBAEV et al.
Yield, %
00
Yield, %
100
1
9
8
7
6
5
4
3
2
0
0
0
0
0
0
0
0
90
80
70
60
50
1
0
0
1.0
1.5
2.0
3.0
0 150 160 170 180 190 200
Reactant ratio
Reaction temperature, °С
Fig. 1. Effect of the reactant ratio on the product yield (Т =
60°С, PCO2 = 10 atm, τ = 6 h).
Fig. 2. Effect of temperature on the product yield ([p-chlo-
rophenol] : [sodium ethyl carbonate] = 2 : 1, PCO2 = 10 atm,
τ = 6 h).
1
Yield, %
Yield, %
00
100
1
9
0
0
0
0
9
8
7
6
5
0
0
0
0
8
7
6
5
0
0
0
0
4
5
6
7
8
9
7
8
9
10
11
12
Time, h
Carbon dioxide pressure, atm
Fig. 4. Effect of the reaction time on the product yield ([p-
chlorophenol] : [sodium ethyl carbonate] = 2 : 1, Т =
Fig. 3. Effect of СО pressure on the product yield ([p-
2
chlorophenol] : [sodium ethyl carbonate] = 2 : 1, Т =
190°С, PCO2 = 10 atm).
190°С, τ = 6 h).
for the carboxylation of p-chlorophenol with sodium
ethyl carbonate, the yield of 5-chloro-2-hydroxyben-
zoic acid is 86.1%.
The results of the investigation of the effect of the
reaction conditions for the carboxylation of p-chloro-
phenol with sodium ethyl carbonate on the product
yield are presented in Figs. 1–4. The optimum ratio of
the reactants is [p-chlorophenol] : [sodium ethyl car-
bonate] = 2 : 1 (Fig. 1). The dependence of the yield of
the product (5-chloro-2-hydroxybenzoic acid) on the
reaction temperature is presented in Fig. 2. When
increasing the temperature from 160 to 190°С, the
product yield increases from 67.0 to 86.1%; a further
increase in the temperature slightly affects the yield of
As is seen, all of the dependence curves for the yield
of the product (5-chloro-2-hydroxybenzoic acid) on
the reaction conditions (temperature, СО pressure,
2
reaction time, reactant ratio) are nonmonotonic in
character. The nonmonotonic pattern of the curves for
the relations of the product yield to the reaction tem-
perature and time are apparently due to side reactions,
such as decarboxylation, occurring at high tempera-
the desired product. The optimum values of pressure tures (above 190°С) and a long reaction time (over
and reaction time are 10 atm and 6 h, respectively 6 h). The nonmonotonic character of the depen-
(
Figs. 3, 4). Under the optimum reaction conditions dences of the product yield on the carbon dioxide
PETROLEUM CHEMISTRY
Vol. 57
No. 5
2017

CARBOXYLATION OF o-, m-, AND p-CHLOROPHENOLS
Carboxylation of m-chlorophenol with sodium ethyl carbonate
Reaction conditions
439
Yield of 4-chloro-
2-hydroxybenzoic
acid, wt %
Ser. no.
reactant ratio
[
m-chlorophenol] : [sodium temperature, °C СО pressure, atm
time, h
2
ethyl carbonate]
1
2
3
4
5
6
8
9
1 : 1
2 : 1
3 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
2 : 1
165
165
165
160
175
165
165
165
165
10
10
10
10
10
8
6
6
6
6
6
6
6
7
5
52.7
76.2
45.2
68.7
62.0
73.3
73.6
60.9
52.1
12
10
10
11
pressure and the reactant molar ratio has not been 7.05 ppm (J = 1.9 Hz), respectively. The proton in the
unambiguously explained yet.
4-position manifests itself as a doublet of doublets at
6
.97 ppm (J = 8.5 and 2.0 Hz). The protons of the car-
The possibility for the use of sodium ethyl carbon-
ate as the carboxylating agent in the carboxylation
reaction of m- and o-chlorophenols was explored. The
carboxylation of m-chlorophenol with sodium ethyl
carbonate proceeds regioselectively to form 4-chloro-
boxylic and hydroxyl groups manifest themselves as a
diffused signal at 10.6 ppm because of strong hydrogen
1
bonding. The H NMR spectra of 4-chloro-2-
hydroxybenzoic and 3-chloro-2-hydroxybenzoic acids
synthesized also correspond to their structures.
2
-hydroxybenzoic acid. The effect of the reaction con-
In summary, the possibility for the use of sodium
ethyl carbonate as the carboxylating agent in the reac-
tion of carboxylation of o-, m-, and p-chlorophenols
has been demonstrated. It has been found that the car-
boxylation of all the chlorophenols with sodium ethyl
carbonate proceeds regioselectively to form 5-chloro-
ditions on the yield of the product was studied (table).
Under the reaction optimum conditions found ([m-
chlorophenol] : [sodium ethyl carbonate] = 2 : 1, Т =
1
65°С, P
= 10 atm, τ = 6 h), the yield of 4-chloro-
CO2
2
-hydroxybenzoic acid reaches 76.2%.
The carboxylation reaction of o-chlorophenol with 2-hydroxybenzoic, 4-chloro-2-hydroxybenzoic, and
sodium ethyl carbonate also proceeds regioselectively 3-chloro-2-hydroxybenzoic acids, respectively. The
to form 3-chloro-2-hydroxybenzoic acid in a substan- optimum conditions for conducting the process
tially lower yield as compared to p- and m-chlorophe- were found. The developed simple and convenient
nols. The carboxylation of o-chlorophenol under the procedures for the synthesis of 5-chloro-, 4-chloro-,
optimum conditions ([o-chlorophenol] : [sodium and 3-chloro-2-hydroxybenzoic acids can be used in
ethyl carbonate] = 2 : 1, Т = 190°С, PCO2 = 10 atm, τ = laboratory and industrial synthesis.
6
h) gives the product (3-chloro-2-hydroxybenzoic
acid) in a yield of 68.2%.
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Translated by E. Boltukhina
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Vol. 57
No. 5
2017