Method for producing dichlorophenylthioglycolic acid

The present invention is directed to a method for producing dichlorophenylthioglycolic acid which comprises reacting monobromodichlorobenzene or trichlorobenzene with a thioglycolate in a ratio of 0.5 to 2.5 mols of the latter to 1 mol of the former in a polar solvent, and to a method for producing dichlorophenylthioglycolic acid comprising further reacting the reaction mixture obtained as above with a monohalogenoacetate. The method of the present invention is very useful industrially, advantageously producing dichlorophenylthioglycolic acid in high yield.

FIELD OF THE INVENTION 
The present invention relates to a method for producing 
dichlorophenylthioglycolic acid. 
Dichlorophenylthioglycolic acid is a compound which is useful as an 
intermediate for thioindigo pigments, chemicals for the electronic 
industry, pharmaceuticals and agricultural chemicals. 
BACKGROUND OF THE INVENTION 
The conventional methods for producing dichlorophenylthioglycolic acid are 
as follows: 
(1) The method in which trichlorobenzene and sodium hydrosulfide are 
reacted at 125.degree. C. under increased pressure in liquid ammonia 
solvent in the presence of copper acetate catalyst for 10 hours to yield 
dichlorothiophenol, which is then reacted with sodium monochloroacetate to 
yield dichlorophenylthioglycolic acid with a yield of 14 to 29% [Kogyo 
Kagaku Zasshi, 70, 1384 (1967)]. 
(2) The method in which dichlorobenzene is sulfonylchlorinated with 
chlorosulfuric acid and then reduced with a large amount of zinc powder 
under acidic conditions to yield dichlorothiophenol, which is then reacted 
with monochloroacetic acid to yield dichlorophenylthioglycolic acid with a 
yield of 81% (U.S. Pat. No. 3,440,288). 
However, these known methods respectively have the following drawbacks. 
In the method of (1) above, the use of liquid ammonia, which is difficult 
to handle, a difficult-to-dispose copper compound and an increased 
reaction pressure poses an operational problem. In addition, the yield is 
low. 
In the method of (2) above, the process spans a long period, and a large 
amount of waste effluent which contains harmful heavy metals can cause 
environmental pollution. 
As stated above, both the known methods have various problems and are not 
industrially advantageous. For this reason, attempts have been made to 
develop an industrially advantageous method for production in the relevant 
technical field, but there is no satisfactory method. 
SUMMARY OF THE INVENTION 
It is an object of the present invention to provide a method for producing 
dichlorophenylthioglycolic acid industrially advantageously with high 
yield. 
Taking note of the situation described above, the present inventors 
conducted investigations to provide a method for producing 
dichlorophenylthioglycolic acid industrially advantageously with high 
yield under mild reaction conditions without using harmful heavy metals. 
As a result, the present inventors have found that a 
dichlorophenylthioglycolate can be produced by reacting 
monobromodichlorobenzene or trichlorobenzene with a thioglycolate as shown 
in the following reaction scheme A. 
Also, in the above-mentioned reaction, when the thioglycolate was added in 
excess of equivalent in order to increase the yield of a 
dichlorophenylthioglycolate, on the contrary the yield of the desired 
product dichlorophenylthioglycolate declined. 
With respect to this phenomenon, the inventors conducted further 
investigations and found that when a thioglycolate is added in excess of 
equivalent, the reaction between the resulting dichlorophenylthioglycolate 
and the unreacted thioglycolate proceeds preferentially as shown in the 
reaction scheme B to yield a dichlorothiophenol salt and thus gives a 
mixture of dichlorophenylthioglycolate and dichlorothiophenol salt. On the 
other hand, when a monohalogenoacetate is added to this reaction mixture, 
the dichlorothiophenol salt changes easily to the 
dichlorophenylthioglycolate in accordance with the reaction scheme C. The 
inventors thus found that the yield improves in comparison with the 
production of a dichlorophenylthioglycolate in a single process in 
accordance with the reaction scheme A, and developed the present 
invention. 
##STR1## 
wherein X represents a chlorine atom or bromine atom; M represents an 
alkali metal. 
Developed on the basis of these findings, the present invention relates to: 
(1) a method for producing dichlorophenylthioglycolic acid which comprises 
reacting monobromodichlorobenzene or trichlorobenzene with a thioglycolate 
in a ratio of 0.5 to 2.5 mols of the latter to 1 mol of the former in a 
polar solvent, and 
(2) a method for producing dichlorophenylthioglycolic acid which comprises 
further reacting the reaction mixture obtained from the reaction of (1) 
above with a monohalogenoacetate. 
DETAILED DESCRIPTION OF THE INVENTION 
The monobromodichlorobenzenes which can serve as a starting material for 
the present invention are exemplified by 1-bromo-2,5-dichlorobenzene, 
1-bromo-2,4-dichlorobenzene, 1-bromo-3,4-dichlorobenzene, 
1-bromo-2,3-dichlorobenzene, 1-bromo-2,6-dichlorobenzene and 
1-bromo-3,5-dichlorobenzene. The trichlorobenzenes which can serve as a 
starting material for the present invention are exemplified by 
1,2,4-trichlorobenzene, 1,2,3-trichlorobenzene and 1,3,5-trichlorobenzene. 
Reaction of monobromodichlorobenzene or trichlorobenzene with a 
thioglycolate is carried out normally in a polar solvent. The polar 
solvent used is not subject to limitation. Examples of polar solvents 
which can be used in the present invention include ethylene glycol, 
diethylene glycol, methanol, ethanol, butanol, N-methyl-2-pyrrolidone, 
N,N-dimethylformamide, N,N-dimethylacetamide, acetamide, formamide, 
caprolactam, 1,1-ethylenedipyrrolidone, tetramethylurea, 
hexamethylphosphoramide, acetonitrile, quinoline, pyridine, lutidine, 
picoline, dimethylsulfoxide, sulfolane and sulfolene, with preference 
given to dimethylsulfoxide, ethylene glycol, N-methyl-2-pyrrolidone, 
sulfolane and the like because they offer a high yield of the reaction 
product dichlorophenylthioglycolic acid. 
The amount of solvent used is 1 to 20 times, preferably 1 to 10 times the 
amount by weight of the starting trichlorobenzene or 
monobromodichlorobenzene. Two or more of the solvents mentioned above may 
be used in combination. 
The amount of thioglycolate used for the present invention is normally 0.5 
to 2.5 times the molar amount of monobromodichlorobenzene or 
trichlorobenzene. Molar ratios below 0.5 result in an increase of 
unreacted monobromodichlorobenzene or trichlorobenzene. When the 
thioglycolate is used at a molar ratio exceeding about 1.0, preference is 
given to the method in which the side product dichlorothiophenol salt is 
converted to the dichlorophenylthioglycolate by the addition of a 
monohalogenoacetate from the viewpoint of improvement in the yield of the 
desired product dichlorophenylthioglycolic acid for the reason described 
above. However, the use of a thioglycolate in a molar ratio exceeding 2.5 
is not advantageous because the increased side production of a 
dichlorophenylthiophenol salt necessitates the addition of a still greater 
amount of a monohalogenoacetate. 
A usable thioglycolate is produced by reacting thioglycolic acid with an 
alkali metal hydroxide or alkali metal carbonate. The thioglycolate 
described above can also be prepared in the reaction system. The alkali 
metal hydroxide or alkali metal carbonate used in this case is exemplified 
by sodium hydroxide, potassium hydroxide, sodium carbonate, sodium 
hydrogen carbonate, potassium carbonate or potassium hydrogen carbonate. 
The amount is suitably 1.6 to 3.0 times the molar amount of thioglycolic 
acid. 
In the present invention, the reaction temperature for the reaction of 
monobromodichlorobenzene or trichlorobenzene with a thioglycolate is 
preferably 50.degree. to 220.degree. C., more preferably 80.degree. to 
190.degree. C. Temperatures below 50.degree. C. result in too low reaction 
rates; temperatures above 220.degree. C. can cause yield reductions due to 
side reactions. The reaction time is preferably 1 to 6 hours; reaction 
times longer than 6 hours can result in yield reductions due to side 
reactions. 
When the monohalogenoacetate is added to the reaction mixture, the 
monohalogenoacetate can include sodium monochloroacetate, potassium 
monochloroacetate, sodium monobromoacetate and potassium monobromoacetate. 
The amount added is normally 1.0 to 4.0 times the molar amount of the 
resulting dichlorothiophenol salt. 
The reaction temperature for the reaction of a dichlorothiophenol salt with 
a monohalogenoacetate is preferably 10.degree. to 200.degree. C., more 
preferably 50.degree. to 120.degree. C. A reaction time of 1 hour is 
sufficient because the rate of the reaction of a dichlorothiophenol salt 
and a monohalogenoacetate is high. By acidizing the resulting reaction 
mixture, the dichlorophenylthioglycolate can easily be converted to 
dichlorophenylthioglycolic acid. In the present invention, when 
trichlorobenzene is used to obtain a 2,5-dichlorophenylthioglycolate, the 
solvent is distilled off, after which the reaction mixture is heated in 
the presence of water and cooled for crystallization to separate the side 
product isomeric 2,4-dichlorophenylthioglycolate. This procedure causes 
crystallization of a 2,5-dichlorophenylthioglycolate alone, which is then 
acidized as above to yield 2,5-dichlorophenylthioglycolic acid with high 
purity. Examples of the acid used for the acidization include hydrochloric 
acid, sulfuric acid, nitric acid and phosphoric acid. The amount added is 
normally 1.0 to 4.0 times, preferably 1.0 to 3.0 times the molar amount of 
dichlorophenylthioglycolate. 
In accordance with the present invention, a dichlorophenylthioglycolate or 
a mixture of dichlorophenylthioglycolate and dichlorothiophenol salt can 
be obtained by reacting monobromodichlorobenzene or trichlorobenzene with 
a thioglycolate under normal pressure. Also, dichlorophenylthioglycolic 
acid can be obtained industrially advantageously in high yield by the very 
simple procedure of reacting this mixture with a monohalogenoacetate.

EXAMPLES 
The present invention is hereinafter described in more detail by means of 
the following working examples and comparative example, but the invention 
is not limited by these examples. 
EXAMPLE 1 
To a 300 ml four-necked flask equipped with a stirrer, a thermometer and a 
condenser were charged 24.9 g (0.110 mol) of 1-bromo-2,5-dichlorobenzene, 
13.19 g (0.143 mol) of thioglycolic acid, 12.06 g (0.286 mol) of 95% 
sodium hydroxide and 100 g of dimethylsulfoxide, followed by stirring at 
120.degree. C. for 4 hours. Then, after distilling off the 
dimethylsulfoxide under reduced pressure, 100 g of water was added to the 
residue. After dissolving the residue therein at 100.degree. C., the 
solution was cooled for crystallization and filtered to yield sodium 
2,5-dichlorophenylthioglycolate, which was then dissolved in 100 g of 
water with heating and acidized with concentrated hydrochloric acid, 
filtered and dried to yield 19.6 g of a light yellowish white powder of 
2,5-dichlorophenylthioglycolic acid. The yield based on 
1-bromo-2,5-dichlorobenzene was 75.1%. 
EXAMPLE 2 
To a 300 ml four-necked flask equipped with a stirrer, a thermometer and a 
condenser were charged 24.9 g (0.110 mol) of 1-bromo-2,5-dichlorobenzene, 
13.19 g (0.143 mol) of thioglycolic acid, 12.06 g (0.286 mol) of 95% 
sodium hydroxide and 100 g of dimethylsulfoxide, followed by stirring at 
120.degree. C. for 4 hours. After cooling until 100.degree. C., 
2,5-dichlorothiophenol salt produced as the side product was treated with 
5.13 g (0.044 mol) of sodium monochloroacetate at the same temperature for 
1 hour. Then, after distilling off the dimethylsulfoxide under reduced 
pressure, 100 g of water was added to 54.5 g of the residue. After 
dissolving the residue therein at 100.degree. C., the solution was cooled 
for crystallization and filtered to yield sodium 
2,5-dichlorophenylthioglycolate, which was then dissolved in 100 g of 
water with heating and acidized with concentrated hydrochloric acid, 
filtered and dried to yield 23.5 g of a light yellowish white powder of 
2,5-dichlorophenylthioglycolic acid. The yield based on 
1-bromo-2,5-dichlorobenzene was 90.0%. 
EXAMPLE 3 
15.4 g of a light yellowish white powder of 2,5-dichlorophenylthioglycolic 
acid was obtained in the same manner as in Example 1 except that the 
1-bromo-2,5-dichlorobenzene was replaced with 20.0 g (0.110 mol) of 
1,2,4-trichlorobenzene. The yield based on 1,2,4-trichlorobenzene was 
59.0%. 
EXAMPLE 4 
19.3 g of a light yellowish white powder of 2,5-dichlorophenylthioglycolic 
acid was obtained in the same manner as in Example 2 except that the 
1-bromo-2,5-dichlorobenzene was replaced with 20.0 g (0.110 mol) of 
1,2,4-trichlorobenzene. The yield based on 1,2,4-trichlorobenzene was 
74.0%. 
EXAMPLES 5 through 7 
2,5-dichlorophenylthioglycolic acid was obtained in the same manner as in 
Example 4 except that reaction temperature, molar ratio of thioglycolic 
acid and reaction time were changed as shown in Table 1. The results are 
shown in Table 1. 
TABLE 1 
__________________________________________________________________________ 
Thioglycolic Reaction 
acid/Halogeno- 
temp. Yield of 
Thioglycolic 
benzene Reaction 
Monohalogeno- 
Dichlorophenyl- 
Ex Halogenobenzene 
acid (molar ratio) 
Solvent 
time acetate tioglycolic 
__________________________________________________________________________ 
acid 
##STR2## 13.19 g (0.143 mol) 
1.3 Dimethyl- sulfoxide 100 g 
120.degree. C. 4 Hr. 
-- 75.1% 
2 
##STR3## 13.19 g (0.143 mol) 
1.3 Dimethyl- sulfoxide 100 g 
120.degree. C. 4 Hr. 
ClCH.sub.2 CO.sub.2 Na 5.13 g 
(0.044 mol) 
90.0% 
3 
##STR4## 13.19 g (0.143 mol) 
1.3 Dimethyl- sulfoxide 100 g 
120.degree. C. 4 Hr. 
-- 59.0% 
4 
##STR5## 13.19 g (0.143 mol) 
1.3 Dimethyl- sulfoxide 100 g 
120.degree. C. 4 Hr. 
ClCH.sub.2 CO.sub.2 Na 5.13 g 
(0.044 mol) 
74.0% 
5 
##STR6## 5.06 g (0.055 mol) 
0.7 Dimethyl- sulfoxide 100 g 
100.degree. C. 6 Hr. 
-- 55.7% 
6 
##STR7## 13.19 g (0.143 mol) 
1.3 Dimethyl- sulfoxide 100 g 
140.degree. C. 3 Hr. 
ClCH.sub.2 CO.sub.2 Na 5.13 g 
(0.044 mol) 
72.1% 
7 
##STR8## 12.15 g (0.132 mol) 
1.2 Dimethyl- sulfoxide 100 g 
120.degree. C. 5 Hr. 
ClCH.sub.2 CO.sub.2 Na 5.13 g 
(0.044 mol) 
70.4% 
__________________________________________________________________________ 
EXAMPLE 8 
To a 500 ml flask equipped with a thermometer, a condenser and a stirrer 
were added 45.2 g (0.2 mol) of 1-bromo-2,5-dichlorobenzene, 23.7 g (0.4 
mol) of 95% potassium hydroxide, 18.4 g (0.2 mol) of thioglycolic acid and 
320 g of N-methyl-2-pyrrolidone, followed by stirring at 140.degree. to 
150.degree. C. for 2 hours. Assay of the reaction solution by high 
performance liquid chromatography identified the solution as a mixture of 
dichlorophenylthioglycolate and dichlorothiophenol salt. Then, after 
distilling off the solvent, 300 g of water and 50 g of toluene were added 
for layer separation. To the water layer was added 45 g of concentrated 
hydrochloric acid, and the mixture was cooled to room temperature. The 
resulting crystal was filtered and dried to yield 28.7 g of 
2,5-dichlorophenylthioglycolic acid. Its melting point was 129.degree. to 
131.degree. C., and the yield was 60.5%. The results are given in Table 2. 
EXAMPLE 9 
Using the same procedure as in Example 8, 45.2 g (0.2 mol) of 
1-bromo-2,5-dichlorobenzene, 23.7 g (0.4 mol) of 95% potassium hydroxide, 
18.4 g (0.2 mol) of thioglycolic acid and 320 g of N-methyl-2-pyrrolidone 
were added, followed by stirring at 140.degree. to 150.degree. C. for 2 
hours. Then, 30.4 g (0.26 mol) of sodium monochloroacetate was added to 
the reaction solution, followed by stirring at 90.degree. C. for 1 hour. 
After distilling off the solvent, 300 g of water and 50 g of toluene were 
added for layer separation. To the water layer was added 45 g of 
concentrated hydrochloric acid, and the mixture was cooled to room 
temperature. The resulting crystal was filtered and dried to yield 34.0 g 
of 2,5-dichlorophenylthioglycolic acid with a yield of 71.7%. The results 
are given in Table 2. 
EXAMPLES 10 THROUGH 13 
Using the combinations of monobromodichlorobenzene or trichlorobenzene, 
thioglycolic acid, potassium hydroxide and solvent listed in Table 2, the 
reaction was carried out in the same manner as in Example 8 or 9 to yield 
2,5-dichlorophenylthioglycolic acid. The results are given in Table 2. 
TABLE 2 
__________________________________________________________________________ 
Thioglycolic Reaction 
acid/Halogeno- temp. Yield of 
Thioglycolic 
benzene Reaction 
Monohalogeno- 
Dichlorophenyl- 
Ex Halogenobenzene 
acid (molar ratio) 
Solvent 
time acetate tioglycolic 
__________________________________________________________________________ 
acid 
##STR9## 18.4 g (0.2 mol) 
1.0 N-methyl-2- pyrrolidone 320 
140.about. 150.degree. C. 2 
--. 60.5% 
9 
##STR10## 
18.4 g (0.2 mol) 
1.0 N-methyl-2- pyrrolidone 320 
140.about. 150.degree. C. 2 
ClCH.sub.2 CO.sub.2 Na 30.4 g 
(0.26 mol) 
71.7% 
10 
##STR11## 
36.8 g (0.4 mol) 
2.0 Ethylene Glycol 80 g 
150.degree. C. 2 Hr. 
-- 41.2% 
11 
##STR12## 
36.8 g (0.4 mol) 
2.0 Ethylene Glycol 80 g 
150.degree. C. 2 Hr. 
ClCH.sub.2 CO.sub.2 Na 30.4 g 
(0.26 mol) 
73.3% 
12 
##STR13## 
25.8 g (0.28 mol) 
1.4 Sulfolane 320 g 
160.degree. C. 3 Hr. 
-- 41.5% 
13 
##STR14## 
25.8 g (0.28 mol) 
1.4 Sulfolane 320 g 
160.degree. C. 3 Hr. 
BrCH.sub.2 CO.sub.2 Na 20.9 g 
(0.13 mol) 
54.5% 
__________________________________________________________________________ 
COMATIVE EXAMPLE 
In the same manner as in Example 8, 45.2 g (0.2 mol) of 
1-bromo-2,5-dichlorobenzene, 23.7 g (0.4 mol) of 95% potassium hydroxide, 
18.4 g (0.2 mol) of thioglycolic acid and 320 g of n-decane were added, 
followed by stirring at 140.degree. to 150.degree. C. for 10 hours. Assay 
of the reaction solution by high performance liquid chromatography 
detected no peak of 2,5-dichlorophenylthioglycolic acid or 
2,5-dichlorothiophenol. Then, 200 g of water was added to the reaction 
solution, and the mixture was cooled to room temperature. Assay of the 
n-decane solution by the high performance liquid chromatography revealed 
that 1-bromo-2,5-dichlorobenzene remained unreacted in an amount 
equivalent to 98.7% of the starting material.