Intermediates for producing 5,7-dichloro-4-hydroxyquinoline

An industrially advantageous process for producing 5,7-dichloro-4-hydroxyquinoline (DCHQ) useful as an intermediate for agrohorticultural bactericides. The process comprises (i) hydrolyzing 3-cyano- or 3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline into 5,7-dichloro-3-carboxy-4-hydroxyquinoline (DCQA) in the presence of hydrochloric, sulfuric or phosphoric acid and (ii) decarboxylating the formed DCQA into DCHQ in the presence of sulfuric or phosphoric acid. In particular, this process comprises continuously conducting the hydrolysis of 5,7-dichloro-3-ethoxycarbonyl-4-hydroxyquinoline and the decarboxylation of the hydrolyzate in the presence of sulfuric acid having a specified concentration. The invention also relates to a process for producing DCQA by hydrolyzing 3-cyano- or 3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline in the presence of hydrochloric, sulfuric or phosphoric acid and a process for producing DCHQ by decarboxylating DCQA in the presence of sulfuric or phosphoric acid.

This application is the national phase of PCT/JP95/00293, filed Feb. 27, 
1995. 
TECHNICAL FIELD 
The present invention relates to a process for producing 
5,7-dichloro-4-hydroxyquinoline (hereinafter, referred to as DCHQ) by 
decarboxylating 5,7-dichloro-3-carboxy-4-hydroxyquinoline (hereinafter, 
referred to as DCQA) in the presence of an acid; to a process for 
producing DCQA by hydrolyzing 3-cyano- or 
3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline in the presence of an 
acid; to a process for producing DCHQ by successively decarboxylating DCQA 
formed in the above hydrolysis in the presence of an acid; and to certain 
intermediates for those manufacturing processes. 
BACKGROUND ART 
Japanese Unexamined Patent Publication No. Hei 1-246263 (JP Laid Open 
Appln. No. 246263/1989) discloses that 
5,7-dichloro-4-(4-fluorophenoxy)quinoline shows an excellent plant 
fungicidal activity as an agrohorticultural bactericide. With respect to a 
process for producing said 5,7-dichloro-4-(4-fluorophenoxy)quinoline, 
there is disclosed a manufacturing process wherein a reaction product of 
3,5-dichloroaniline and Meldrum's acid is heated to produce DCHQ, the 
resulting DCHQ is made to react with phosphorus oxychloride to produce 
4,5,7-trichloroquinoline and the resulting 4,5,7-trichloroquinoline is 
made to react with 4-fluorophenol. In the manufacture of DCHQ in the 
above-mentioned process, it is usually conducted that 3,5-dichloroaniline 
is made to react with Meldrum's acid to produce 
2,2-dimethyl-4,6-dioxo-5-(3,5-dichloroanilinomethylene)-1,3-dioxane and 
the resulting 
2,2-dimethyl-4,6-dioxo-5-(3,5-dichloroanilinomethylene)-1,3-dioxane is 
thermally cyclized to give DCHQ. In addition to said process, it is also 
conducted, for example, that 3,5-dichloroaniline is made to react with 
diethyl ethoxymethylenemalonate to produce 
5,7-dichloro-3-ethoxycarbonyl-4-hydroxyquinoline, the resulting 
5,7-dichloro-3-ethoxycarbonyl-4-hydroxyquinoline is hydrolyzed with an 
aqueous solution of sodium hydroxide to produce DCQA and the resulting 
DCQA is decarboxylated on heating at 240.degree.-250.degree. C. to give 
DCHQ. 
However, in the prior art processes, there are difficulties in their 
industrial utilizations that (i) especially in hydrolysis of 
5,7-dichloro-3-ethoxycarbonyl-4-hydroxyquinoline, although the reaction 
time is short, the produced DCQA is of a very fine crystal whereby its 
separation is difficult resulting in a poor productivity; and (ii) the 
process requires a large quantity of heating medium for decarboxylation of 
DCQA. In addition, it is difficult to obtain a large amount of Meldrum's 
acid in low cost. Therefore, there has been a demand for a manufacturing 
process which is suitable for industrial utilization using a material 
available easier than Meldrum's acid. 
The present inventors have conducted an investigation for overcoming the 
difficulties in the prior art processes, particularly the drawback which 
is inherent in the prior art process where diethyl ethoxymethylenemalonate 
is used, with particular attention for an improvement in effectively 
conducting the hydrolysis of 
5,7-dichloro-3-ethoxycarbonyl-4-hydroxyquinoline and the decarboxylation 
of DCQA and also in conducting the decarboxylation of DCQA without the use 
of heating medium whereupon a process for producing DCHQ which is suitable 
for industrial utilization has been achieved. 
DISCLOSURE OF THE INVENTION 
One aspect of the present invention is: 
(i) a process for producing 5,7-dichloro-4-hydroxyquinoline (DCHQ) which 
comprises decarboxylating 5,7-dichloro-3-carboxy-4-hydroxyquinoline (DCQA) 
in the presence of sulfuric acid or phosphoric acid; 
(ii) a process for producing DCHQ which comprises hydrolyzing 3-cyano- or 
3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline in the presence of 
hydrochloric acid, sulfuric acid or phosphoric acid followed by subjecting 
the resulting 5,7-dichloro-3-carboxy-4-hydroxyquinoline (DCQA) to a 
decarboxylation as mentioned in the above process (i); and 
(iii) a process for producing DCHQ according to the above-mentioned process 
(ii) in which hydrolysis and decarboxylation are continuously conducted in 
the presence of sulfuric acid or phosphoric acid. 
Another aspect of the present invention is: 
(iv) a process of producing DCQA which comprises hydrolyzing 3-cyano- or 
3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline in the presence of 
hydrochloric acid, sulfuric acid or phosphoric acid; 
(v) a process of producing DCHQ which comprises 
(a) condensing 3,5-dichloroaniline with ethyl orthoformate or ethyl 
cyanoacetate, 
(b) subjecting the resulting ethyl 1-cyano-2-(3,5-dichloroanilino)acrylate 
to a thermal cyclization and 
(c) then subjecting the resulting 3-cyano-5,7-dichloro-4-hydroxyquinoline 
to the above-mentioned process (ii) or (iv) and; 
(vi) certain intermediates for the above-mentioned producing processes. 
According to those processes, crystals of DCQA can be easily separated from 
the reaction products of the hydrolysis and also DCQA can be favorably 
decarboxylated without a heating medium. Furthermore, there is no need of 
separating the DCQA after hydrolysis but decarboxylation can be 
continuously carried out. Thus, many advantages can be resulted for the 
industrial utilization. 
DETAILED DESCRIPTION OF THE INVENTION 
5,7-Dichloro-3-ethoxycarbonyl-4-hydroxyquinoline which is used as a 
starting material in the process of the present invention may be readily 
manufactured by thermal cyclization of a reaction product of 
3,5-dichloroaniline with diethyl ethoxymethylenemalonate. It is also 
possible to readily manufacture 5,7-dichloro-3-cyano-4-hydroxyquinoline by 
thermal cyclization of a reaction product of 3,5-dichloroaniline with 
ethyl orthoformate and ethyl cyanoacetate. 
Production of 3-cyano- or 3-acetyl-5,7-dichloro-4-hydroxyquinoline is 
generally conducted as follows: 
3,5-Dichloroaniline, ethyl orthoformate and ethyl cyanoacetate or ethyl 
acetoacetate which are all easily available in industry are used as 
starting materials for the instant process and, generally, those materials 
are thermally condensed in the presence of a heating medium which is inert 
to the reaction and in an atmosphere of nitrogen gas. Amounts of those 
materials used are not necessarily specified because they are dependent 
upon the reaction conditions and reaction devices but, usually, 0.8-3.0 
moles (preferably, 1.0-1.5 moles) of ethyl orthoformate and 0.8-3.0 moles 
of ethyl cyanoacetate or ethyl acetoacetate (preferably, 1.0-1.5 moles of 
ethyl cyanoacetate) are used to one mole of 3,5-dichloroaniline. Reaction 
temperature is usually from 70.degree. to 200.degree. C., and preferably 
from 90.degree. to 170.degree. C. 
The above-mentioned heating medium may include those which are inert to the 
reaction, those which are not decomposed in the condensation and the like. 
Examples of the above-mentioned heating medium are alkylnaphthalenes, 
diphenyl, diphenyl ether, alkyl diphenyls, triphenyl hydride, etc. They 
may be used either solely or jointly. More specific examples are Therm-S 
200, 300, 600, 700, 800 and 900 (trade names; manufactured by Nippon Steel 
Chemical Co., Japan) and Dowtherm A (trade name; manufactured by The Dow 
Chemical Co., USA). Among them, Therm-S 300 (trade name; manufactured by 
Nippon Steel Chemical Co., Japan) and Dowtherm A (trade name; manufactured 
by The Dow Chemical Co., USA) are preferred. Amounts of the heating medium 
are not necessarily specified but, usually, from 50 to 500 parts by 
weight, and preferably from 100 to 260 parts by weight, to 100 parts by 
weight of 3,5-dichloroaniline. 
As a condensation proceeds, ethanol is usually by-produced and it is 
removed outside of the reaction system by evaporation. As such, the 
condensation usually finishes within from 3 to 15 hours to give ethyl 
1-cyano-2-(3,5-dichloroanilino)acrylate or ethyl 
1-acetyl-2-(3,5-dichloroanilino)acrylate. The condensation product is 
subjected to conventional steps of purification and separation whereupon 
the above-mentioned acrylate can be readily obtained. Thus, for example, 
the condensation product is crystallized by diluting with a solvent such 
as ethanol or isopropanol. Then the crystals of the acrylate separated out 
therefrom were filtered, if necessary, followed by washing with the 
above-mentioned solvent to give said acrylate with a high purity. 
Next, ethyl 1-cyano- or ethyl 1-acetyl-2-(3,5-dichloroanilino)acrylate is 
thermally cyclized to give 3-cyano- or 
3-acetyl-5,7-dichloro-4-hydroxyquinoline. Cyclization is usually conducted 
in the presence of a heating medium. Thus, for example, the acrylate is 
added either gradually or in portions to a previously-heated heating 
medium with stirring and the reaction is conducted paying such an 
attention that the occurrence of the side reaction is made as little as 
possible throughout that period. With respect to a heating medium, those 
which are the same as those used in the above condensation may be used. 
The amount of the heating medium is not necessarily specified but it is 
usually from 200 to 2,000 parts by weight, and preferably from 500 to 
1,500 parts by weight, to 100 parts by weight of the acrylate. The 
cyclization is usually conducted at the reaction temperature of 
200.degree.-260.degree. C., and preferably at 240.degree.-260.degree. C. 
for 5-20 hours. The cyclization is carried out by removing the heating 
medium and by-produced ethanol from the reaction system by evaporation. 
Similarly to the case of the above-mentioned condensation product, when 
the cyclization product is subjected to the conventional purifying and 
separating steps, 3-cyano-5,7-dichloro-4-hydroxyquinoline or 
3-acetyl-5,7-dichloro-4-hydroxyquinoline is readily obtained. 
Alternatively, 3,5-dichloroaniline, ethyl orthoformate and ethyl 
cyanoacetate or ethyl acetoacetate may be thermally condensed so that the 
cyclization of the resulting condensation product is carried out 
continuously or simultaneously whereupon 3-cyano- or 
3-acetyl-5,7-dichloro-4-hydroxyquinoline is obtained favorably. In that 
case, the reaction may be carried out without isolation and purification 
of the condensation product, and/or with care so that occurrence of the 
side reaction is made as little as possible. Amounts of the starting 
materials and their ratio, heating temperature, type and amount of the 
heating medium used, etc. may be suitably selected. When 
3-cyano-5,7-dichloro-4-hydroxyquinoline is subjected to hydrolysis and 
decarboxylation in accordance with the present invention, it can be 
smoothly converted to DCHQ but 3-acetyl-5,7-dichloro-4-hydroxyquinoline 
can be also converted to DCHQ by subjecting to a deacetylation which is 
usually conducted for acetyl-substituted aromatic compounds. 
In the present invention, 3-cyano- or 
3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline is mixed with 
hydrochloric acid, sulfuric acid or phosphoric acid with heating whereupon 
the hydrolysis usually takes place. Concentration and amount of 
hydrochloric acid, sulfuric acid or phosphoric acid used here are not 
necessarily specified because of their dependency on type of the starting 
materials, reaction temperature, reaction device, etc. Usually, however, 
the concentration of hydrochloric acid is 5-35%, and preferably 20-35%, 
and that of sulfuric acid and phosphoric acid is 5-85%, and preferably 
50-70%, while its amount to one mole of the starting 3-cyano- or 
3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline is 3-50 moles, and 
preferably 3-25 moles. Temperature for the hydrolysis is not, again, 
necessarily specified but it is usually from 70.degree. to 200.degree. C., 
and preferably from 80.degree. to 150.degree. C. The reaction time is from 
0.5 to 10 hours. When 3-cyano- or 
3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline is used as a starting 
material and is hydrolyzed, ammonia or ethanol is by-produced, 
respectively but ammonia can be neutralized with the acid in the reaction 
system to give an ammonium salt of the acid while ethanol can be easily 
removed from the reaction system by distillation during the hydrolysis. 
At the stage where hydrolysis is completed in the present invention, the 
resulting DCQA is once separated from the reaction products and then 
subjected either to a decarboxylation of DCQA or, without separating the 
DCQA, to a hydrolysis followed by a decarboxylation. When DCQA is 
separated from the reaction product, common purifying and separating 
operations may be applied to the hydrolysis products. Thus, for example, 
the reaction products are cooled, poured into water and stirred to produce 
crystals followed by subjecting to a simple solid-liquid separation to 
give DCQA smoothly. 
In the present invention, the decarboxylation is usually conducted by 
mixing DCQA with sulfuric acid or phosphoric acid with heating. 
Concentration and amount of sulfuric acid or phosphoric acid are not 
necessarily specified but the concentration is usually from 5 to 85%, 
preferably from 50 to 85%, and more preferably from 50 to 70%, and the 
amount to one mole of DCQA is from 3 to 50 moles, and preferably from 3 to 
25 moles. This decarboxylation is usually completed at 
100.degree.-200.degree. C., and preferably at 120.degree.-170.degree. C., 
within 1-24 hours and, during the decarboxylation, carbon dioxide gas is 
removed from the reaction system. 
In conducting the hydrolysis and decarboxylation in the process according 
to the present invention, a suitable combination of type, concentration 
and amount of the acid is selected. For example, the hydrolysis is carried 
out using diluted hydrochloric acid and then the decarboxylation is 
conducted using 50-70% sulfuric acid; the hydrolysis is carried out using 
5-50% sulfuric acid or 5-50% phosphoric acid and then the decarboxylation 
is carried out using 50-70% sulfuric acid or 50-70% phosphoric acid by 
adding higher concentration of sulfuric acid or phosphoric acid thereto; 
or the hydrolysis and decarboxylation are continuously carried out using 
50-70% sulfuric acid as from the initial stage. Among those three, the 
latter method is most preferred in view of reaction operations and 
reaction efficiency. When the decarboxylation product is subjected to 
common purifying and separating steps, desired DCHQ can be readily 
obtained. For example, the decarboxylation product is cooled and poured 
into water to crystallize the DCHQ and then the crystals are filtered and 
washed with water, with an aqueous alkali solution such as sodium 
hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate, 
or with alcohol such as ethanol and isopropanol. As a result, the desired 
DCHQ can be recovered, for example, with a purity of 97% and with a yield 
of not less than 94%. In accordance with the present invention, it is also 
possible that said hydrolysis and decarboxylation are conducted in the 
same reaction system whereby the desired DCHQ is favorably obtained. 
Further in accordance with the present invention, the desired DCHQ may be 
also obtained favorably by conducting said hydrolysis and decarboxylation 
continuously for forming a heterogeneous reaction phase in the same 
reaction system.

EXAMPLES 
Described below are examples of the present invention which are provided 
only for illustrative purposes. 
Example 1. (Manufacture of 5,7-Dichloro-4-hydroxyquinoline) 
5,7-Dichloro-3-ethoxycarbonyl-4-hydroxyquinoline (114.4 g; 0.4 mole) and 
572 g of 62.5% sulfuric acid were charged in a 1,000 ml four-necked flask 
equipped with stirrer, thermometer and distilling tube and the mixture was 
heated with stirring at 120.degree. C. Ethanol which was by-produced 
during the reaction was evaporated outside the reaction system and the 
reaction was conducted by heating the reactants at 140.degree. C. for 
three hours. The reaction mixture was analyzed by means of liquid 
chromatography whereupon it was found that the starting 
5,7-dichloro-3-ethoxycarbonyl-4-hydroxyquinoline disappeared while 
5,7-dichloro-3-carboxy-4-hydroxyquinoline in 78% yield and 
5,7-dichloro-4-hydroxyquinoline in 22% yield were produced. 
After the distilling tube was changed to a reflux condenser and the 
reaction mixture was heated to 145.degree.-150.degree. C., the reaction 
was conducted by heating the reaction mixture for 12 hours more. The 
reaction products were analyzed by liquid chromatography whereupon it was 
found that 5,7-dichloro-3-carboxy-4-hydroxyquinoline disappeared while 
5,7-dichloro-4-hydroxyquinoline in 99% yield was produced. 
The reaction product was poured into 572 g of cold water to form crystals 
of 5,7-dichloro-4-hydroxyquinoline followed by filtration. The crystals 
were washed with water and dried to give 82.1 g of 
5,7-dichloro-4-hydroxyquinoline (purity: 99%; yield: 95%). 
Example 2. (Manufacture of 5,7-Dichloro-4-hydroxyquinoline) Manufacture of 
5,7-Dichloro-3-cyano-4-hydroxyquinoline (A) 
(A-1). Ethyl orthoformate (15.6 g; 0.1 mole), 12.2 g (0.1 mole) of ethyl 
cyanoacetate, 16.2 g (0.1 mole) of 3,5-dichloroaniline and 28 ml of 
Therm-S 300 (trade name; a heating medium; manufactured by Nippon Steel 
Chemical Co., Japan) were charged in a 300 ml four-necked flask and the 
mixture was stirred. The temperature of the mixture was elevated to 
96.degree. C. during one hour together with introduction of nitrogen gas, 
then gradually raised with evaporation of the generated ethanol and 
elevated up to 160.degree. C. during about 1.5 hours more. The reaction 
was conducted at 160.degree.-170.degree. C. for 7 hours. The end point of 
the reaction was confirmed by analyzing the content in the flask by means 
of liquid chromatography. The reaction product was crystallized by 
diluting with 300 ml of isopropanol and the separated crystals were 
filtered at 25.degree. C. and washed with 120 ml of isopropanol to give 
25.6 g of ethyl 2-(3,5-dichloroanilino)-1-cyanoacrylate. Its melting point 
was 179.degree.-180.degree. C., the purity as analyzed by liquid 
chromatography was 99.99% and the yield based upon a 3,5-dichloroaniline 
group was 89.5%. 
(A-2). Therm-S 300 (120 ml; a heating medium) was charged in a 300 ml 
four-necked flask equipped with a water separator and stirred. Into the 
stirred Therm-S 300 with heating at 253.degree.-254.degree. C. was poured 
10 g (0.035 mole) of ethyl 2-(3,5-dichloroanilino)-1-cyanoacrylate in 
portions during seven hours and the reaction was continued by evaporating 
the heating medium and the by-products at 254.degree.-255.degree. C. for 
three hours more. The end point of the reaction was confirmed by liquid 
chromatography (distilled amount of ethanol was 8.2 ml). The reaction 
product was cooled at 90.degree. C., crystallized by adding 30 ml of 
isopropanol thereto and the separated crystals were filtered at 20.degree. 
C. and washed with 30 ml of isopropanol to give 8.2 g of 
5,7-dichloro-3-cyano-4-hydroxyquinoline. This crystal was pale brown. The 
purity as a result of analysis by liquid chromatography was 98.1% and the 
yield based upon ethyl 2-(3,5-dichloroanilino)-1-cyanoacrylate was 98.1%. 
Manufacture of 5,7-Dichloro-3-cyano-4-hydroxyquinoline (B) 
(B-1). Ethyl orthoformate (15.6 g; 0.1 mole), 12.2 g (0.1 mole) of ethyl 
cyanoacetate, 16.2 g (0.1 mole) of 3,5-dichloroaniline and 42 ml of 
Therm-S 300 (a heating medium; trade name; manufactured by Nippon Steel 
Chemical Co., Japan) were charged in a 300 ml four-necked flask and the 
mixture stirred. The temperature of the mixture was elevated to 96.degree. 
C. during one hour together with introduction of nitrogen gas, gradually 
raised together with evaporation of generating ethanol and elevated up to 
160.degree. C. during 1.5 hours more and the reaction was conducted at 
160.degree.-170.degree. C. for seven hours. The end point of the reaction 
was confirmed by analyzing the content in the flask using liquid 
chromatography for checking the disappearance of the starting 
3,5-dichloroaniline. 
After completion of the reaction, the temperature in the flask was allowed 
to drop to 150.degree. C. and low-boiling fractions (such as unreacted 
ethyl cyanoacetate) boiling together with Therm-S 300 were evaporated 
(distilled amount: 17 ml) whereupon a solution of ethyl 
2-(3,5-dichloroanilino)-1-cyanoacrylate in Therm-S 300 was obtained. This 
solution was analyzed by liquid chromatography whereupon it contained 26.3 
g of ethyl 2-(3,5-dichloroanilino)-1-cyanoacrylate (the yield based upon 
3,5-dichloroaniline: 92%). 
(B-2). Therm-S 300 (a heating medium) (316 ml) was charged in a 1,000 ml 
four-necked flask equipped with stirrer, thermometer and water separator 
and stirred. To the stirred Therm-S 300 was added dropwise a solution of 
ethyl 2-(3,5-dichloroanilino)-1-cyanoacrylate in Therm-S 300 prepared in 
the above (B-1) during ten hours with heating at 253.degree.-254.degree. 
C., and the reaction was further conducted by evaporating the heating 
medium and the by-products at 254.degree.-255.degree. C. for two hours. 
The end point of the reaction was confirmed by liquid chromatography. The 
end point of the reaction was checked by confirming the disappearance of 
ethyl 2-(3,5-dichloroanilino)-1-cyanoacrylate (Distilled amount including 
ethanol was 33 ml.). The reaction product was cooled at 90.degree. C., 
crystallized by adding 80 ml of isopropanol thereto, cooled at 30.degree. 
C., filtered and washed with 80 ml of isopropanol to give 21.5 g of 
5,7-dichloro-3-cyano-4-hydroxyquinoline. This crystal was pale brown and 
its purity analyzed by liquid chromatography was 97.8% while its yield 
based upon 3,5-dichloroaniline was 90.0%. 
Manufacture of 5,7-Dichloro-4-hydroxyquinoline 
5,7-Dichloro-3-cyano-4-hydroxyquinoline (7.0 g; 0.0293 mole) and 104 g of 
62.5% sulfuric acid were charged in a 300 ml four-necked flask equipped 
with stirrer, thermometer and reflux condenser, and the mixture was heated 
up to a boiling point (144.degree.-146.degree. C.) during one hour and 
subjected to a reaction at the same temperature for 15 hours. When the 
reaction product was analyzed by liquid chromatography, 
5,7-dichloro-4-hydroxyquinoline was produced in 99% yield (where the 
starting 5,7-dichloro-3-cyano-4-hydroxyquinoline disappeared while an 
intermediate, 5,7-dichloro-3-carboxy-4-hydroxyquinoline, was produced in 
not more than 0.2% yield). 
The reaction product was cooled to 110.degree. C. and allowed to 
crystallize 5,7-dichloro-4-hydroxyquinoline by adding 104 g of water 
gradually thereto followed by filtering. The crystals were washed with 
water and further washed with 20 ml of isopropanol to give 5.93 g of 
5,7-dichloro-4-hydroxyquinoline (purity: 99.88%; yield: 94.6%). 
Example 3 (Manufacture of 5,7-Dichloro-4-hydroxyquinoline) 
5,7-Dichloro-3-ethoxycarbonyl-4-hydroxyquinoline (114.4 g; 0.4 mole) and 
343.2 g of 70% sulfuric acid were charged in a 1,000 ml four-necked flask 
equipped with stirrer, thermometer and distilling tube and the mixture was 
heated at 150.degree. C. with stirring. Reaction was continued by heating 
up to 165.degree. C. during three hours together with evaporation of the 
by-produced ethanol outside the reaction system. The reaction product was 
analyzed by liquid chromatography whereupon and it was found that the 
starting 5,7-dichloro-3-ethoxycarbonyl-4-hydroxy-quinoline disappeared and 
that 5,7-dichloro-3-carboxy-4-hydroxyquinoline in 22% yield and 
5,7-dichloro-4-hydroxyquinoline in 78% yield were produced. 
After the distilling tube was changed to a reflux condenser and the 
reaction mixture was heated to 165.degree.-175.degree. C., the reaction 
was conducted with heating for seven hours more. The reaction product was 
analyzed by liquid chromatography whereupon 
5,7-dichloro-3-carboxy-4-hydroxyquinoline disappeared and 
5,7-dichloro-4-hydroxyquinoline was produced in 99% yield. 
The reaction product was cooled to 100.degree. C., crystallized by adding 
258 g of water gradually thereto, cooled to 30.degree. C. and filtered. 
The crystals were poured into 600 g of water, heated at 
40.degree.-45.degree. C., neutralized with aqueous 48% sodium hydroxide 
with stirring to pH 3-4, filtered at 30.degree. C., washed with water, 
further washed with 80 ml of isopropanol and dried to give 84.0 g of 
5,7-dichloro-4-hydroxyquinoline (purity: 99%; yield: 98%). 
Example 4. (Manufacture of 5,7-Dichloro-3-acetyl-4-hydroxyquinoline) 
(1) The same operations as in Example 2 (A-1) were conducted for the 
manufacture of 5,7-dichloro-3-cyano-4-hydroxyquinoline (A) in the 
above-mentioned Example 2 except that 13 g (0.1 mole) of ethyl 
acetoacetate was used instead of 12.2 g (0.1 mole) of ethyl cyanoacetate 
to give 26.0 g of ethyl 2-(3,5-dichloroanilino)-1-acetylacrylate. The 
purity of this product analyzed by liquid chromatography was 98.9% and the 
yield based upon 3,5-dichloroaniline was 86.0%. 
(2) Then the same operations as in Example 2 (A-2) were conducted except 
that 10.6 g (0.035 mole) of ethyl 2-(3,5-dichloroanilino)-1-acetylacrylate 
was added in a divided manner during six hours instead of 10 g (0.035 
mole) of ethyl 2-(3,5-dichloroanilino)-1-cyanoacrylate of Example 2 (A-2) 
to give 8.7 g of 5,7-dichloro-3-acetyl-4-hydroxyquinoline. This crystal 
was pale yellow and the purity analyzed by liquid chromatography was 99.0% 
while the yield based upon 2-(3,5-dichloroanilino)-1-acetylacrylate was 
97.0%. 
MERIT OF THE INVENTION 
In accordance with the present invention, 3-cyano- or 
3-ethoxycarbonyl-5,7-dichloro-4-hydroxyquinoline is hydrolyzed in the 
presence of hydrochloric acid, sulfuric acid or phosphoric acid to give 
5,7-dichloro-3-carboxy-4-hydroxyquinoline (DCQA) and, when the resulting 
product is decarboxylated in the presence of sulfuric acid or phosphoric 
acid, 5,7-dichloro-4-hydroxyquinoline (DCHQ) can be readily manufactured. 
In the present invention, DCQA can be smoothly and advantageously 
separated from the hydrolysis intermediates. Moreover, there is no need of 
using a heating medium in the decarboxylation. It is also possible that 
both hydrolyzing and decarboxylating reactions can be continuously carried 
out without separating 5,7-dichloro-3-carboxy-4-hydroxyquinoline during 
the reactions.