DE1695231B1 - 3-carbalkoxy-4-hydroxy-quinoline derivatives - Google Patents

Description

wherein R ₁ denotes an alkyl group with 12 to 14 carbon atoms or a benzyl group optionally substituted by 1 or 2 chlorine atoms, R ₂ denotes a methyl or ethyl group and R ₃ denotes a hydrogen atom or an alkyl group with 1 to 6 carbon atoms or an alkoxy group with 1 to 4 carbon atoms .

2.3 - Carbomethoxy - 4 - hydroxy - 6 - η - butyl-7-benzyloxy-quinoline.

3. 3 - Carbomethoxy - 4 - hydroxy - 6 - η - propyl-7-n-dodecyloxy-quinoline.

4. 3 - Carbomethoxy - 4 - hydroxy - 6 - η - propyl-7-benzyloxy-quinoline.

5. 3 - Carbomethoxy - 4 - hydroxy - 6 - ethoxy-7-benzyloxy-quinoline.

6. 3-carbethoxy -4-hydroxy-6-n -propoxy-7-benzyloxy-quinoline.

7. 3-Carbomethoxy-4-hydroxy-6-n-propoxy-7-benzyloxy-quinoline.

8.3 Carbomethoxy - 4 - hydroxy - 6 - isopropoxy-7-benzyloxy-quinoline.

9. 3 - Carbomethoxy - 4 - hydroxy - 6 - η - propyl-7- (4'-chlorobenzyloxy) -quinoline.

10. 3 - Carbomethoxy - 4 - hydroxy - 6 - η - propyl-7- (2'-chlorobenzyloxy) -quinoline.

11. A method for the preparation of the compounds according to claim 1, characterized in that one in a manner known per se either

a) a compound of the general formula

N = CH-CH (COOR ₂ );

■ 2Λ2

heated or
b) an acid of the general formula

OH

COOH

or a halide of such an acid is reacted with an alcohol of the general formula R ₂ OH.

12. Veterinary medicinal product, consisting of a compound according to claim 1 and non-toxic diluent or carriers.

The invention relates to 3-carbalkoxy-4-hydroxyquinoline derivatives the general formula

b) an acid of the general formula

COOR,

wherein R ₁ denotes an alkyl group with 12 to 14 carbon atoms or a benzyl group optionally substituted by 1 or chlorine atoms, R ₂ denotes a methyl or ethyl group and R ₃ denotes a hydrogen atom, an alkyl group with 1 to 6 carbon atoms or an alkoxy group with 1 to 4 carbon atoms.

The compounds of general formula I are prepared by being known per se Way either

a) a compound of the general formula

II

R ₁ 0 N = CH - CH (COOR ₂ ) ₂

heated or

45 or a halide of such an acid with an alcohol of the general formula R ₂ OH.

The cyclization according to procedure a) can, for. B. expedient by heating the starting material above 200 ° C. The cyclization reaction can be carried out in the presence of an inert diluent or solvents, e.g. B. Diphenyl ether or the eutectic mixture of diphenyl and Diphenyl ether.

The reaction of an alcohol of the general formula R ₂ OH with an acid of the general formula III can be carried out in the presence of a mineral acid, e.g. B. sulfuric acid or hydrochloric acid, take place as a catalyst. Acid chloride, for example, can be used as the acid halide.
The compounds of general formula I according to the invention have a valuable activity against coccidiosis. Their coccidiosis-preventing properties are particularly directed against the intestinal genus Eimeria brunetti, and some of the

Compounds are effective against the appendix genera Eimeria tenella and Eimeria necatrix. she can therefore be used as active ingredients in veterinary medicinal products for the prophylaxis of coccidiosis in poultry or others Pets are used.

Various compounds of the invention have been tested for effectiveness against coccidiosis compared with known, equally effective compounds using the following method:

The compound under investigation was dispersed evenly in a common chick feed, and medical feeds were prepared containing the compound to be tested in concentrations contained from 0.1 to 0.0001%. Groups of eight 9 day old chicks each were with the medicated feeds were fed for 7 days, and two control chick groups were fed non-medicated feeds Lining fed. Every chick except those in one of the control groups was given

infected with a sufficient number of Eimeria tenella oocysts to protect all of the untreated chicks Killing the control group, which required approximately 50,000 to 400,000 oocysts. At the end of the 7 day trial period, the number of chicks killed in each group was recorded and in addition, the mean weight gain per chick in each group. From a trial connection was believed to have an effect against coccidiosis at a certain concentration if significantly fewer chicks were killed in the treated group than in the infected group Control group and if the weight gain of the chicks in the treated group is comparable was with that of the uninfected control group.

With various compounds according to the invention, those listed in the table below were compiled Get results.

R ₂ R ₃ concentration Number of those killed in the Weight gain in grams of the ■ chicks in the not
infected in the
Feed chick infected infected Control R ₁ Weight treated group treated group group CH ₃ nC ₃ H ₇ O percent group group 49.2 CH ₃ nC ₃ H ₇ 0.003 8th 4.0 46.7 Ci ₂ H ₂₅ CH ₃ H 0.0008 0 8th 34.5 2.2 55.0 Ci ₂ H ₂₅ CH ₃ H 0.006 0 6th 41.2 13.5 42.0 Ci ₂ H ₂₅ C ₂ H ₅ nC ₃ H ₇ 0.006 0 7th 51.2 14.6 30.7 Benzyl CH ₃ nC ₃ H ₇ 0.003 0 6th 40.5 12.2 37.7 Benzyl C ₂ H ₅ nC ₄ H ₉ 0.0008 0 7th 37.0 10.3 42.9 Benzyl CH ₃ nC ₄ H ₉ 0.003 0 8th 42.5 17.5 46.5 Benzyl CH ₃ CH ₃ O 0.0005 0 8th 42.0 9.9 48.2 Benzyl CH ₃ C ₂ H ₅ O 0.003 0 6th 48.2 13.5 48.2 Benzyl C ₂ H ₅ nC ₃ H ₇ O 0.0004 0 6th 44.7 13.5 46.5 Benzyl CH ₃ nC ₃ H ₇ O 0.0005 0 8th 44.7 9.9 48.2 Benzyl CH ₃ ISO-C ₃ H ₇ O 0.0008 0 6th 47.6 13.5 55.7 Benzyl CH ₃ nC ₃ H ₇ 0.0008 0 8th 49.0 5.7 44.0 Benzyl CH ₃ nC ₃ H ₇ 0.0004 0 8th 51.0 9.2 47.8 p-chlorobenzyl CH ₃ nC ₃ H ₇ 0.0004 0 8th 44.8 7.5 49.0 o-chlorobenzyl 0.0015 0 8th 58.7 9.2 2,4-dichloro 0 46.7 benzyl

The same tests were carried out with the following two commercially available compounds: Connection 1:

S-carbomethoxy ^ -hydroxy-oJ-di-isopropoxy-quinoline. Connection 2:

S-Carboethoxy ^ -hydroxy-oJ-di-isobutoxy-quinoline.
The test results obtained with these compounds are summarized in the following table:

concentration Number of chicks killed in the infected Weight gain in grams of the chicks
in the infected not infected in feed treated group treated group group Weight percent group 8th group 12.7 46.8 0.01 1 8th 48.8 0.006 3 8th 34.0 0.003 6th 8th 18.5 12.7 46.8 0.01 0 8th 52.6 0.006 1 8th 49.4 0.003 2 8th 40.0 0.0015 4th 25.0

Toxicity

When the test compounds were added to the feed in concentrations of up to 0.1%, neither had the compounds According to the invention, the products on the market still result in the death of the chicks.

In the case of veterinary medicinal products, the active ingredient is mixed with inert diluents, e.g. B. kaolin, talc, calcium carbonate, Fuller's earth, attapulgite clay or oyster shell meal, or with a feed as a diluent, such as B. Ground grain, dried brewery grain, wheat fodder meal or corn meal, mixed. These masses should be coordinated so that they can be further diluted with a feed can direct to an appropriate medical feed, the poultry or other domestic animals can eat. Preferably contain such medicinal feed masses directly from Poultry can be eaten, about 0.00005 to about 0.1 percent by weight active ingredient, in particular 0.0001 to 0.001 percent by weight of active ingredient, based on the total feed. The veterinary drugs contain preferably about 0.1 to about 25 percent by weight of active ingredient, in particular 0.1 to 2 percent by weight Active ingredient.

The invention is explained in more detail by the following exemplary embodiments, all quantitative data are based on weight.

example 1

There are 93 parts of 3-benzyloxyanilinomethylene malonic acid - Diethyl ester gradually added to 450 parts of boiling diphenyl ether. The mixture is refluxed for 30 minutes and then cooled. The solid product is filtered off with carbon tetrachloride washed and off. Dimethylformamide recrystallized. 3-Carbethoxy-4-hydroxy-7-benzyloxy-quinoline is obtained; Mp 295 ° C; Yield 34%.

The 3-Benzyloxyanilinomethylenmalonsäurediäthylester used as starting material can be prepared as follows: A mixture of 45 parts of 3-benzyloxyaniline and 51 parts Äthoxymethylenmalonsäurediäthylester is heated for 1 hour at 100 ⁰ C. The solid reaction product is recrystallized from ethanol. Diethyl 3-benzyloxyanilinomethylene malonate is obtained; F. 7 Γ C.

Example 2

Crude 3-n-dodecyloxyanilmomethylene malonic acid diethyl ester, by heating 17 parts of 3-n-dodecyloxyaniline and 13.5 parts of diethylethoxymethylene malonic acid diethyl ester has been maintained at 200 ° C for 2 hours gradually becomes 100 parts added to boiling diphenyl ether. The mixture is refluxed for 30 minutes and then cooled. The solid product is filtered off, washed with carbon tetrachloride and made from dimethylformamide recrystallized. 3-Carbethoxy-4-hydroxy-7-n-dodecyloxy-quinoline is obtained; Mp 255 ° C; Yield 69%.

Example 3

Crude 3 - benzyloxyanilinomethylene malonic acid dimethyl ester, obtained by heating 4 parts for 2 hours 3-benzyloxyaniline and 3.5 parts of dimethyl methoxymethylene malonate has been obtained, is gradually boiling to 40 parts with stirring Diphenyl ether added. The mixture is stirred and refluxed for 30 minutes and then cooled down. The solid product is filtered off, washed with carbon tetrachloride and made from dimethylformamide recrystallized. 3-carbomethoxy-4-hydroxy-7-benzyloxy-quinoline is obtained; M.p. 273 C; Yield 80%.

Example 4

Crude 3-benzyloxy-4-η-propylanilinomethylene malonic acid diethyl ester, which has been obtained by heating 3.5 parts of 3-benzyloxy-4-n-propylaniline and 3.4 parts of ethoxymethylene malonic acid diethyl ester for 2 hours, is added all at once to 35 parts of boiling diphenyl ether with stirring . The mixture is stirred and refluxed for 5 minutes and then cooled. The solid product is filtered off, recrystallized with petroleum ether (bp. 40 to 60 ⁰ C) and dried from dimethylformamide. S-carbethoxy- ^ hydroxy-6-n-propyl-7-benzyloxy-quinoline is obtained; Mp 299 ° C; Yield 45%.

The 3-benzyloxy-4-n-propylaniline used to prepare the starting material can be prepared as follows: A mixture of 10 parts of 3-hydroxy-4-n-propylacetanilide, 7.2 parts of benzyl chloride, 20 parts of potassium carbonate and 120 parts of acetone is Heated under reflux for 18 hours. After cooling and filtering the mixture, the filtrate is evaporated under reduced pressure. The evaporation residue is dissolved in chloroform and the solution is washed successively with a dilute sodium hydroxide solution and a saturated sodium chloride solution. The chloroform solution is then evaporated and dried, and the residue is recrystallized from petroleum ether (60 to 8O ⁰ C Kp.). 3-Benzyloxy-4-n-propylacetaniline is obtained; F. 85 ^° C. 9 parts of this compound are then heated under reflux for 6 hours with 20 parts of potassium hydroxide in a mixture of 10 parts of water and 100 parts of ethanol. The solution is then cooled and evaporated, under reduced pressure, and the residue is partitioned into water and ether. The ethereal layer is separated, washed with saturated sodium chloride solution, dried and evaporated. 3-Benzyloxy-4-n-propylaniline is obtained as an oil.

Example 5

The process according to Example 4 is repeated with the difference that the 3.4 parts of ethoxymethylene malonic acid diethyl ester are replaced by 2.7 parts of methoxymethylene malonic acid dimethyl ester. S-carbomethoxy ^ -hydroxy-one-propyl-7-benzyloxy-quinoline is obtained; M.p. 292 ^° C; Yield 27%.

Example 6

The solid acid chloride of 3-carboxy-4-hydroxy-7-benzyloxyquinoline, which has been obtained as indicated below, is refluxed with 50 parts of dry methanol for 1 hour, whereupon the solution is evaporated. The solid residue is mixed with 50 parts of water and the mixture is heated to 100 ° C. for a few minutes and then cooled and filtered. The solid product is recrystallized from dimethylformamide. This gives 3-carbomethoxy - 4 - hydroxy - 7 - benzyloxy - quinoline; M.p. 273 ^D C; Yield 80%.

The acid chloride of S-carboxy- ^ hydroxy-T-benzyloxy-quinoline used as starting material can be prepared as follows: A mixture of 34 parts of 3-carbethoxy-4-hydroxy-7-benzyloxy-quinoline and 200 parts of a solution of 10 parts by weight Potassium hydroxide in 100 parts by volume of water is refluxed for 2 hours. Some charcoal is added and the hot mixture is filtered. The filtrate is acidified with hydrochloric acid, whereupon the precipitated solid product is filtered off, washed with water, dried in vacuo at 100 ° C. for 18 hours and recrystallized from 2-ethoxyethanol. This gives 3-carboxy-4-hydroxy-7-benzyloxy-quinoline; F. 273 ⁰ C.

A mixture of 5 parts of 3-carboxy-4-hydroxy-7-benzyloxy-quinoline and 35 parts of thionyl chloride is refluxed for 2 hours, mixed with a catalytic amount of pyridine. The excess thionyl chloride is evaporated, whereupon 25 parts of benzene are added and the Mixture is evaporated to dryness.

Example 7

According to the process according to Example 6, des 3-carboxy-4-hydroxy-6 is obtained from the acid chloride - η - pr opy 1 - 7 - benzyloxy - quinolines 3 - carbomethoxy-4 - hydroxy - 6 - η - propyl - 7 - benzyloxy - quinoline; F. 292 ° C.

The 3-carboxy-4-hydroxy-6-η-propyl-7-benzyloxyquinoline used to prepare the starting material can be prepared as follows: A mixture of 5.5 parts of 3-carbethoxy-4-hydroxy-6-n-propylbenzyloxy quinoline and 45 parts of a solution of 10 parts by weight of sodium hydroxide in 100 parts by volume of water is refluxed for 2 hours. Some charcoal is added and the warm mixture is filtered. The filtrate is acidified with hydrochloric acid, whereupon the precipitated solid matter is filtered off, washed with water and ^{dried in vacuo at 100 °} C. for 18 hours. This gives 3-carboxy-4-hydroxy-6-n-propyl-7-benzyloxy-quinoline; F. 271 ⁰ C.

Example 8

8 parts of 3-n-dodecyloxyanilinomethylene malonic acid dimethyl ester (F. 58 ° C), by heating 8 parts of 3-n-dodecyloxyaniline and 4.5 parts for 2 hours Dimethyl methoxymethylene malonate to 100 ° C. and recrystallization of the solid reaction product from petroleum ether (boiling point 40 to 60 ° C.) is added to 80 parts of boiling diphenyl ether. The mixture is refluxed for 20 minutes and then cooled. Then it becomes solid Product heated in boiling carbon tetrachloride, then cooled and filtered. The solid Product is recrystallized from dimethylformamide. This gives S-carbomethoxy ^ -hydroxy ^ -n-dodecyloxy-quinoline; Mp 255 ° C; Yield 57%.

Example 9

1 part of 3-carboxy-4-hydroxy-7-benzyloxy-quinoline is mixed with 1 part of concentrated sulfuric acid in 50 parts absolute ethanol heated under reflux for 24 hours. The cooled solution is diluted with water, and the precipitated solid is washed with alcohol and recrystallized from dimethylformamide. This gives 3-carbethoxy-4-hydroxy-7-benzyloxy-quinoline; Mp 295 ° C; Yield 67%.

Example 10

Crude 3 - (4 '- chlorobenzyloxy) - 4 - η - propylanilinomethylene malonic acid dimethyl ester, by heating a mixture of 7.6 parts of 3- (4'-chlorobenzyloxy) -4-n-propylaniline and 5.7 parts for 2 hours Methoxymethylene malonic acid dimethyl ester to 100 ° C and subsequent cooling has been obtained, becomes 48 parts of a boiling eutectic mixture of diphenyl and diphenyl ether with stirring given. The solution is stirred and refluxed for 5 minutes and then cooled. That the resulting crystalline product is filtered off, washed with methanol and extracted from dimethylformamide recrystallized. This gives 3-carbomethoxy-4-hydroxy-6-n-propyl-7- (4'-chlorobenzyloxy) -quino- lin; Mp 295 ° C; Yield 33%.

3-Carbethoxy-4-hydroxy-6-η-propyl-7- (4'-chlorobenzyloxy) -quinoline is obtained in the same way, mp 299 ° to 301 ° C., yield 50%, 3-carbomethoxy-4-hydroxy -6-n-propyl-7- (2'-chlorobenzyloxy) -quinoline, m.p. 283 ° C, yield 33%, and 3-carbomethoxy-4 - hydroxy - 6 - η - propyl - 7 - (2 ' , 4 '- dichloro-benzyloxy) -quinoline, F. 299 ° C, yield 40%, and 3-carbomethoxy -A- hydroxy - 6 - η - propyl - 7 - dodecyloxy - quinoline, F. 256 ⁰ C; Yield 39%.

The 3- (4'-chlorobenzyloxy) -4-n-propylaniline used to prepare the starting material can be used as follows be prepared: A mixture of 7 parts of 4-n-propyl-3-hydroxyacetanilide, 6.6 parts of 4-chlorobenzyl chloride, 14 parts of potassium carbonate and 100 parts of acetone are stirred and refluxed for 18 hours heated. The reaction mixture is filtered while hot and the filtrate is in vacuo evaporated to dryness. The residue is recrystallized from ethanol. This gives 3- (4'-chlorobenzyloxy) -4-n-propylacetanilide; M.p. 112 ° C. This product is then mixed with a solution of 19 parts of potassium hydroxide heated under reflux for 6 hours in 10 parts of water and 115 parts of ethanol. The solvent is then evaporated and the residue is partitioned into ether and water. The essential Solution is made with a 10% sodium hydroxide solution and then with saturated sodium chloride solution washed. It is then dried over magnesium sulfate and then evaporated, whereby 3- (4'-chlorobenzyloxy) -4-n-propylaniline gives as an oil.

3- (2'-chlorobenzyloxy) -4-n-propylaniline is obtained in the same way, M.p. 46 ° C, 3 - (2 ', 4'-dichlorobenzyloxy) - 4 - η - propylaniline and 3 - dodecyloxy-4-n-propylaniline as oil.

Example 11

Crude 3 - benzyloxy - 4 - η - hexylanilinomethylene malonic acid diethyl ester, by heating a mixture of 5.4 parts of 3-benzyloxy-4-n-hexylaniline for 1 hour and 4.4 parts of diethyl ethoxymethylene malonate is obtained under Stirring at once added to 10 parts of boiling diphenyl ether. The mixture is stirred for 5 minutes and heated to reflux and then cooled. The solid product is filtered off with carbon tetrachloride washed and recrystallized from dimethylformamide. This gives 3-carbethoxy-4-hydroxy-6-n-hexyl-7-benzyloxy-quinoline; Mp 283-285 ° C; yield 37%.

3-Carbethoxy-4-hydroxy-6-methyl-7-benzyloxy-quinoline, F. 321 bis, is obtained in the same way

209 519/429

323 ° C, yield 50%, 3 - carbethoxy - 4 - hydroxy-6-n-butyl-7-benzyloxy-quinoline, F. 297 to 298 ⁰ C, yield 18%, 3 - carbomethoxy -A- hydroxy-6- n-hexyl-7-benzyloxy-quinoline, m.p. 278-280 ⁰ C, yield 29%, 3-carbomethoxy-4-hydroxy-6-methyl-7-benzyloxy-quinoline, m.p. 307-309 ⁰ C, yield 25 %, 3 - carbomethoxy - 4 - hydroxy - 6 - ethyl-7-benzyloxy-quinoline, F. 269 to 27O ⁰ C, yield 18%, 3-carbomethoxy-4-hydroxy-6-n-butyl-7-benzyloxy - quinoline, mp 287 to 288 ° C, yield 41%, and 3 - carbomethoxy - 4-hydroxy- 6 - isobutyl - 7 - benzyloxy-quinoline, mp 288 ° C, yield 18%.

The 3-benzyloxy-4-n-hexylaniline used to prepare the starting material can be prepared as follows: A mixture of 17 parts of 3-hydroxy-4-n-hexylacetanilide, 9 parts of benzyl chloride, 15 parts of potassium carbonate and 300 parts of acetone is added for 24 hours Heated to reflux. The mixture is cooled and filtered and the filtrate is evaporated under reduced pressure. The residue was crystallized from methylene chloride mixed with petroleum ether recrystallized (bp 40 to 6O ⁰ C.); F. 90 to 92 ° C. 21 parts of this compound are then refluxed with 63 parts of potassium hydroxide in a mixture of 40 parts of water and 300 parts of ethanol. The solution is then cooled and evaporated under reduced pressure. The residue is distributed in water and ether. The ethereal layer is separated, washed with saturated sodium chloride solution, dried and evaporated. This gives 3-benzyloxy-4-n-hexylaniline as an oil.

Example 12

35

Crude 3 - benzyloxy - 4 - methoxy - anilinomethylene malonic acid dimethyl ester, which has been obtained by heating 3.7 parts of 3-benzyloxy-4-methoxyaniline and 3.0 parts of dimethyl methoxymethylene malonate to 100 ° C. for 3 hours, is carefully added to 21 parts of boiling diphenyl ether with stirring given. The mixture is stirred and refluxed for 3 minutes and then rapidly cooled. The solid product is filtered off, recrystallized with petroleum ether (bp. 40 to 6O ⁰ C) and dried from dimethylformamide. This gives 3-carbomethoxy ^ -hydroxy-o-methoxy ^ -benzyloxy-quinoline; M.p. 287 to 288 ° C; Yield 40%.

3-Carbomethoxy-4-hydroxy-7-benzyloxy-quinoline is obtained in the same way; M.p. 262 to 263 ° C; Yield 25%.

Example 13

7.7 parts of 3 - benzyloxy -A- äthoxyanilinomethylenmalonsäuredimethylester be carefully added with stirring to 30 parts of boiling diphenyl ether. The mixture is stirred and refluxed for 3 minutes and then rapidly cooled. The solid product is filtered off, washed with petroleum ether (boiling point 40 to 60 ° C.) and recrystallized from dimethylformamide. This gives 3-carbomethoxy-4-hydroxy-6-ethoxy-7-benzyloxy-quinoline; M.p. 281 to 282 ° C; Yield 40%.

3-Carbethoxy-4-hydroxy-6-ethoxy-7-benzyloxy-quinoline is obtained in the same way; F. 289 to 290C; Yield 60%.

The 3-benzyloxy-4-ethoxyanilinomethylene malonic acid dimethyl ester used as the starting material can be made as follows: A mixture of

6.1 parts of 3-benzyloxy-4-äthoxyanilin and 4.4 parts of dimethyl methoxymethylenemalonate is refluxed for 2.5 hours at 100 ⁰ C. The mixture is then allowed to cool overnight. The solid reaction product is recrystallized with petroleum ether (bp. 40 to 6O ⁰ C) and dried from methanol. This gives dimethyl 3-benzyloxy-4-ethoxyanilinomethylene malonate; F. 95 to 96 ° C.

The 3-benzyloxy-4-ethoxyaniline can be prepared as follows: A solution of 30 parts of sodium sulfide in 55 parts of water is a solution of 10.5 parts of 3 - benzyloxy - 4 - ethoxynitrobenzene in 140 parts of ethanol are added and the mixture is stirred and refluxed for 16 hours. That Ethanol is distilled off and the residue is extracted with ether. The essential extracts will be dried, filtered and evaporated. This gives 3-benzyloxy-4-ethoxyaniline as an oil.

The 3-benzyloxy-4-ethoxynitrobenzene can be prepared as follows: A mixture of 11 parts 2-benzyloxy-4-nitrophenol, 57 parts of ethyl chloride,

6.2 parts of anhydrous potassium carbonate and 50 parts of dry acetone are stirred for 48 hours and heated under reflux. The mixture is filtered hot and the filtrate is evaporated. The residue is washed with water and then recrystallized from ethanol. This gives 3-benzyloxy-4-ethoxynitrobenzene; F. 101 to 102 ⁰ C.

Example 14

20 parts of 3-benzyloxy-4-η-propoxyanilinomethylene malonic acid diethyl ester are carefully added to 80 parts of boiling diphenyl ether with stirring. The mixture is stirred and refluxed for 11 minutes and then rapidly cooled. The solid product is filtered off, recrystallized with petroleum ether (bp. 40 to 6O ⁰ C) and dried from dimethylformamide. This gives 3-carbethoxy-4-hydroxy-6-n-propoxy-7-benzyloxy-quinoline; Mp 278-279 ° C (decomposition); Yield 72%.

3-Carbomethoxy-4-hydroxy-6-n-propoxy-7-benzyloxy-quinoline is obtained in the same way; M.p. 266 to 267 ^° C; Yield 52%.

The 3 - benzyloxy - 4 - η - propoxyanilinomethylenmalonsäurediäthylester can be prepared as follows: A mixture of 14Teilen 3-benzyloxy-4-n-propoxyaniline and 11.8 parts Äthoxymethylenmalonsäurediäthylester is heated for 2 hours at 100 ⁰ C and then cooled. In this way, 3-benzyloxy-4-η-propoxyanilinomethylene malonic acid diethyl ester is obtained as an oil.

The 3 - benzyloxy - 4 - η - propoxyanilinomethylene malonic acid dimethyl ester can be prepared as follows: A mixture of 9.3 parts of 3-benzyloxy-4-n-propoxyaniline and 63 parts of dimethyl methoxymethylene malonate are heated to 100 ° C. for 2 hours heated. This gives dimethyl 3-benzyloxy-4-n-propoxyanilinomethylene malonate as oil.

Example 15

Crude 3 - η - tetradecyloxyanilinomethylene malonic acid dimethyl ester, that by heating 14.6 parts of 3-n-tetradecyloxyaniline and 6.6 parts for 2 hours Methoxymethylene malonic acid dimethyl ester has been obtained at 100 ° C, is boiling to 100 parts

11 12

Diphenyl ether given. The mixture is 30 minutes Vn-tetradecyloxy-quinoline; M.p. 244 to 246 ^° C; Austen heated to reflux and then cooled. That loots 25%.

solid product is filtered off, with carbon tetrachloride- In the same way, 3-carbethoxy-4-hy-

Washed fabric and recrystallized from dimethylformamide hydroxy-7-n-tetradecyloxy-quinoline; M.p. 243 to 245 ° C;

lized. S-carbomethoxy ^ -hydroxy- 5 yield 39%.

Claims (1)

Patent claims: 1. 3-Carbalkoxy-4-hydroxyquinoline derivatives of the general formula OH
R, ^! COOR ₂ R ₁ O ■ Ν ' ίο