CH621543A5 - Process for the preparation of 3-phenylpyridazone. - Google Patents

Description

The present invention relates to a new process for the preparation of 3-phenylpyridazones which can be used as intermediates for the synthesis of pharmaceuticals and crop protection agents.

It is already known to obtain 3-phenylpyridazone- (6) from the corresponding 4,5-dihydro product by oxidation with elemental bromine (J. Am. Chem. Soc. 75, page 1117, Ber. 32, page 399). The p-Cl-, p-Br- and p-J-phenylpyridazones can also be prepared in an analogous manner. It is also known to obtain aminophenylpyridazones by oxidation of the corresponding 4,5-dihydropyridazones- (6) using nitro-benzenesulfonic acid (DE-OS 1 670 043). However, these production methods are cumbersome and mostly start from the relatively expensive succinic anhydride. The oxidizing agents used (bromine or nitrobenzenesulfonic acid) are also expensive and difficult to handle.

It is also known to prepare 3- (p-methylphenyl) pyridazone (6) by reacting p-methylbenzoylacrylic acid with hydrazine. However, this procedure is unsatisfied

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/ N — NI

// \ = 0, (I)

R1

in which R and R ', which may be the same or different, a 20 hydrogen atom, an alkyl radical with up to 5 C atoms, a cycloalkyl radical, a halogen atom, a nitro group, a hydroxyl group, an O-alkyl group with 1-4 C- Atoms, an OCF3 group, a phenoxy group, an -S-CH3 group, an amino group or R and R 'together represent an alkylene group with 4 C atoms, can be obtained in a simple manner if one during the reaction from an ester of a 3-benzoylacrylic acid of the formula

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in which X represents an alkyl radical with 1-8 C atoms, starts and this ester is reacted with more than 1 mol of hydrazine per mol of compound of the formula II.

The present invention accordingly relates to a 40 process for the preparation of 3-phenylpyridazone (6) of the formula I, which is characterized in that a 3-benzoylacrylic acid ester of the formula II is reacted with more than 1 mol of hydrazine per mole of the compound of the formula II and subjecting the resulting reaction mixture or isolated intermediate to an acid treatment at elevated temperature.

Halogen in the definition R and R 'is to be understood in particular as chlorine, bromine and fluorine.

The reaction according to the invention with ring closure to give pyridazone is particularly surprising because it is known that benzoylacrylic acid is in the trans form (Lutz, J. Am. Chem. Soc. 1930, page 3424) and trans-1,4-carbonyl - Compounds in general with hydrazine do not give a ring closure to form a pyridazine ring.

The esterification of the 3-benzoylacrylic acid can be carried out directly using an excess of the corresponding alcohol by heating, if appropriate with azeotropic abortion of the water formed in the reaction.

But it is also possible to better drive off the water of reaction, an inert solvent, for. B. use benzene.

A preferred embodiment of the esterification, especially when using alcohols with up to 3 carbon atoms, is that the crude benzoylacrylic acid in benzene solution, if appropriate after removal of the water still present, is mixed with an excess of alcohol and the mixture is refluxed and after cooling the separated water separates as the lower layer. The

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Esterification is expediently brought to an end after the addition of a further amount of alcohol by azeotropic expulsion of the water of reaction. After the solvent has been stripped off, the ester of the formula II remains, which can be used directly for the further reaction.

In most cases, a small amount of HCl still available from the Friedel-Crafts reaction to produce the benzoylacrylic acid is sufficient as an esterification catalyst. However, the usual esterification catalysts can also be used.

A preferred embodiment consists in that the reaction is initially carried out in the alkaline reaction region to an intermediate product which can be separated from the reaction mixture. After acidification, this intermediate product quickly reacts when heated to the desired pyridazone of the formula I. It is possible and in some cases advantageous to separate the above-mentioned intermediate product and thus carry out a cleaning operation.

In the process according to the invention, a hydrazine excess compared to the amount theoretically required for pyridazine formation is used. For example, at least 1.5 moles of hydrazine, but preferably 2-4 moles of hydrazine, should be used per mole of compound of formula II originally present.

It is now possible, after the phenylpyridazone of the formula I has been separated off, to release the excess hydrazine in the mother liquor by adding alkali and, after supplementing the spent hydrazine, to carry out the reaction again with the benzoylacrylic acid esterification product. But you can also the hydrazine from the mother liquor, for. B. by formation of a sparingly soluble salt, separate and use for a new implementation.

In general, it is advantageous to use water, an alcohol or a mixture thereof as the reaction medium. However, it is also possible to use other organic solvents which have a certain solubility for the reactants and are inert to them.

The separation of the phenylpyridazone of the formula I obtained, which is normally obtained in good purity, is usually simple, since it has only a very low solubility and crystallizes well. If a particularly high purity is required, compounds of the formula I can easily be purified by recrystallization from mostly polar solvents or by reprecipitation over the alkali metal salts.

The phenylpyridazones which can be obtained in the manner according to the invention are crystallized compounds which are sparingly soluble in water and have melting points above 100.degree.

The percentages below are percentages by weight.

example 1

A crude, benzene benzoylacrylic acid solution, obtained by reacting 10 kg of maleic anhydride with 65 1 techn. Pure benzene using 21 kg of powdered anhydrous A1C13 as a catalyst according to Friedel Crafts, and decomposition with dilute hydrochloric acid, is freed from the water still dissolved by azeotropic distillation. After cooling, 120 g of conc. H2S04 and 8 l of methanol were added. The mixture was refluxed for 3 hours, left to stand overnight, the aqueous layer deposited on the bottom was separated off, a further 5 l of methanol were added and the mixture was boiled for 3 hours. After cooling again, the layers were separated and then the excess methanol was distilled off with the benzene at normal pressure up to a bottom temperature of 91 ° C. The remaining residue had an acid number of 12 mg KOH / g crude ester.

At 20 ° C 50 1 24% aqueous hydrazine hydrate solution was added to the crude ester and stirred for one hour. The temperature of the mixture rose to 70 ° C. After distilling off the remaining amounts of benzene and released methanol, the mixture was cooled to 40 ° C, 24 1 conc. Hydrochloric acid was added, the mixture was brought to boiling temperature and left to reflux for 3 hours. Now it is cooled slightly and the crystals are centrifuged off, washed with water, the filtrate is removed and stored. The crystals are washed again with water. After drying, 17.0 kg of 3-phenylpyridazone- (6) with mp = 192-196 ° C. were obtained which still contained 3% of inorganic impurities. This corresponds to a pure yield of 16.5 kg of phenylpyridazone (6) or 94% of theory, based on maleic anhydride used.

The mother liquor remaining after centrifugation contains hydrazine as the hydrochloride. After concentrating and alkalizing, this solution can be returned to the process.

Example 2

200 g of ethyl p-methylbenzoylacrylate were stirred with 530 ml of 24% hydrazine hydrate solution and 400 ml of water, then boiled for one hour and cooled. 250 ml conc. HCl was added dropwise and then refluxed for an additional 30 minutes. The crystals formed were suction filtered at 20 ° C., washed with water and dried. 150 g yield of 3- (p-methylphenyl) -pyridazone- (6) corresponding to 88.2% of theory to a total. Related to esters. Mp = 224-227 ° C.

calc .: C 70.95 H 5.41 N 15.04 O 8.59%

found: C 70.8 H 5.4 N 15.0 O 8.9%

For example, the starting material is prepared as follows: 185 g of p-methylbenzoylacrylic acid were dissolved in 11 benzene and boiled using a water separator in a reflux condenser. 200 ml of ethanol in which 20 g of HCl had been dissolved were added dropwise and boiled from a dropping funnel until no more aqueous phase was separated off. The mixture was then evaporated in vacuo and the residue was distilled under a fine vacuum. 201.5 g of ethyl p-methylbenzoylacrylate, corresponding to a yield of 95% of theory, were obtained.

Sdpo, 1 mm = 129-131 ° C nD20 = 1.5476 calc .: C 71.54 H 6.47 O 21.99%

found: C 71.9 H 6.9 0 21.5%

Example 3

246 g of ethyl p-chlorobenzoyl acrylate were stirred with 570 ml of 24% hydrazine hydrate solution and 400 ml of water, boiled for 1 hour, then concentrated at 270 ° C. with 270 ml. Acidified HCl and cooked for another 30 minutes. The crystals formed were suction filtered at room temperature, washed with water and dried. 190 g of 3- (p-chlorophenyl) pyridazone (6) are obtained, corresponding to an 89% yield based on the ester used. Mp = 263-264 ° C.

calc .: C 58.12 H 3.41 N 13.56 Cl 17.16 O 7.74% found: C 57.7 H 3.6 N 13.4 Cl 17.0 O 8.4%

251 g of p-chlorobenzoylacrylic acid were boiled with a mixture of 11 benzene and 200 ml of ethanol, which contained 20 g of HCl, until water separation had ended, using a water separator on a reflux condenser. Then the benzene was distilled off in vacuo and the residue was distilled under a fine vacuum. 266 g of ethyl p-chlorobenzoylacrylate were obtained, corresponding to a yield of 94% of theory.

Sdpo, 15 mm = 143-144 ° C Mp = 61-64 ° C calc .: C 60.3 H 4.7 Cl 14.9 0 20.1%

found: C 60.7 H 4.6 Cl 14.8 O 19.8%

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Example 4

210 g of ethyl 3,4-dichlorobenzoyl acrylate were mixed with 500 ml of 24% hydrazine hydrate solution and 400 ml of water and boiled for 1 hour, then 250 ml of conc. HCl added and allowed to continue reacting at boiling heat for one hour. The crystals formed were suction filtered, washed with water and dried. 160 g of 3- (3 ', 4'-dichlorophenyl) pyridazone (6), corresponding to 86.1% of theory, based on the ester used, were obtained. Mp = 243-246 ° C.

calc .: C49.82 H 2.51 N 11.62 Cl 29.42 0 6.63% found: C 49.8 H 2.7 N 11.1 C129, l 0 7.0%

227 g of 3,4-dichlorobenzoylacrylic acid were mixed with a mixture consisting of 11 benzene and 200 ml of ethanol, which contained 20 g of HCl, and boiled over a water separator in a reflux condenser. After the esterification was complete, the benzene was evaporated and the residue was distilled in vacuo.

240 g yield of 3,4-dichlorobenzoylacrylic acid ethyl ester correspond to 95% of theory.

Sdpo 5 mm = 165-168 ° C Mp = 49-54 ° C

Example 5

190 g of 98% hydrazine hydrate were diluted with 400 ml of ethanol and, while stirring, 300 g of the crude p-methoxybenzoylacrylic acid isobutyl ester were added dropwise over the course of 5 minutes and the mixture was boiled for 1 hour. The mixture was then cooled, the crystals were filtered off with suction and the filtrate was evaporated. The residue was stirred with 100 ml of water, the crystals were suction filtered, combined with the first crystals and dried.

Of the 280 g of intermediate thus obtained, 180 g were suspended in 500 ml of water. 100 ml conc. HCl was added, a clear solution only being formed. After boiling for an hour, the precipitated crystals were filtered off with suction at 20 ° C., washed with water, dried and recrystallized from ethanol.

138 g of 3- (4'-methoxphenyl) pyridazone (6) with mp = 189-190 ° C. were obtained. This corresponds to a yield of 93% of theory, based on the p-methoxybenzoylacrylic acid used for the respective stages.

260 g of p-methoxybenzoylacrylic acid were boiled with 400 ml of isobutanol over a water separator until the H20 separation had ended. The excess isobutanol was totally distilled off in a rotary evaporator in vacuo.

The residue obtained was 330 g of crude p-methoxybenzoyl-acrylic acid isobutyl ester in the form of a light yellow oil. A sample distilled in vacuo shows a boiling point of 195-197 ° C at 0.04 mm Hg, nD25 = 1.5460.

calc .: C 68.7 H 6.9 0 24.4%

found: C 68.4 H 7.2 0 24.7%

The 3- (p-methylmercaptophenyl) pyridazone-6 with melting point 208-211 ° C. was prepared analogously to Example 5.

f. C "H10N2OS

fro .: C 60.53 H 4.62 N 12.83 S 14.69%

found: C 59.9 H 4.8 N 13.3 S 14.0%

the 3- (p-n-butoxyphenyl) pyridazone-6 with melting point 178-181 ° C.

f. c14h16n, o2

calc .: C 68.83 H 6.60 N 11.47 0 13.10%

found: C 68.6 H 6.6 Nll, 4 O 13.4%

and the 3- (p-phenoxyphenyl) pyridazon-6 with melting point 177-179 ° C.

f. ci6h, 2n2o2

calc .: C72.71 H 4.58 N 10.60 O 12.11%

found: C 72.5 H 5.0 N 10.5 O 12.3%

Example 6

450 g of p-isopropylbenzoylacrylic acid isobutyl ester were added to a mixture of 250 g of 98% hydrazine hydrate and 500 ml of ethanol over the course of 10 minutes and

Cooked for 2 hours. The mixture was then cooled, the crystals were filtered off with suction and the filtrate was evaporated in vacuo. The residue was stirred with 100 ml of water, suction filtered and the two crystals obtained were combined and dried. Of the 380 g of intermediate thus obtained, 280 g were suspended in 500 ml of water, with 150 ml of conc. Acidified HCl and refluxed for 3 hours. The crystals formed were suction filtered, washed with water and recrystallized from ethanol. 210 g of 3- (p-isopropylphenyl) pyridazone (6) were obtained. This corresponds to a yield of 80% of theory based on the p-isopropylbenzoylacrylic acid used for the respective stage. Mp = 203-205 ° C

calc .: C 72.87 H 6.59 N 13.07 0 7.47%

found: C 73.0 H 6.7 N 13.2 O 7.10%

370 g of p-isopropylbenzoylacrylic acid were esterified with 500 ml of isobutyl alcohol and 460 g of ester were obtained, corresponding to 99% of theory.

Sdpo, 1 mm = 195-200 ° C nD25 = 1.5170 calc .: C 74.7 H 8.05 O 17.5%

found: C 73.4 H 8.4 O 18.2%

Example 7

600 g of crude β-2-tetroyl-acrylic acid isobutyl ester were allowed to flow in the course of 10 minutes into a mixture consisting of 250 g of 98% hydrazine hydrate and 600 ml of ethanol and then boiled for 2 hours. The mixture was then cooled and the crystals formed were suction filtered at 10 ° C., washed with water and ethanol and dried. 290 g of a light yellow crystallizate with mp = 146-200 ° C. were obtained.

290 g of the resulting reaction product of / S-2-tetra-acrylic acid isobutyl ester with hydrazine hydrate were suspended in 500 ml of water, 150 ml of conc. HCl added and

Cooked for 3 hours. Crystals were soon precipitated from the solution, which was almost clear at the beginning. This was suction filtered at 20 ° C, washed with water, recrystallized from alcohol and dried. This gave 180 g of 3 - () 3-tetroyl) -pyrida-zon- (6) corresponding to 40% of theory based on maleic anhydride or tetralin used. Mp = 215-216 ° C calc .: C 74.31 H 6.24 N 12.38 0 7.07%

found: C 74.8 H 6.2 N 12.5 O 6.9%

400 g of anhydrous, powdered A1C13 were suspended in 800 ml of 1,1,2,2-tetrachloroethane, 200 g of maleic anhydride were added, the mixture was stirred for 10 minutes and 264 g of tetralin were added dropwise from a dropping funnel over the course of 10 minutes. The mixture was then stirred for 2 hours and the dark red viscous solution was stirred into 3 l of water. The aqueous phase was then separated off, the organic phase was shaken out again with 500 ml of water and the tetrachloroethane was then distilled off in vacuo. The residue was stirred with toluene and the crystals were suction filtered. There were 530 g of moist beta-tetroyl acrylic acid with mp = 147-148 ° C.

530 g of the crude β-tetroylacrylic acid obtained above were esterified with 500 ml of isobutanol by refluxing over a water separator. The excess isobutanol was distilled off in vacuo. The residue obtained was 603 g of brown-colored crude ester, which could not be distilled in vacuo.

Example 8

400 g of 3,4-dimethylbenzoylacrylic acid were esterified with 11 n-butanol and 2 g of p-toluenesulfonic acid, and then the excess n-butanol was distilled off in vacuo. The crude ester was then allowed to flow into a mixture consisting of 300 g of 98% hydrazine and 800 ml of ethanol.

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Cooked for 2 hours and then cooled to 20 ° C. The crystals were filtered off, washed with water and dried. The intermediate thus obtained was suspended in 11 water, 200 ml conc. HCl was added and the resulting solution was refluxed for 3 hours. The crystals formed in the course of this time were suction filtered after cooling to 20 ° C., washed with water, recrystallized from alcohol and dried.

There were 295 g of 3- (3 ', 4'-dimethylphenyl) pyridazone (6), corresponding to a yield of 78% of theory, based on the 3,4-dimethylbenzoylacrylic acid used. Mp = 255-256 ° C.

calc .: C 71.98 H 6.04 N 13.99 O 7.99%

found: C 72.1 H 6.0 N 14.0 O 7.8%

Example 9

176 g (1 mol) of benzoylacrylic acid were dissolved in 264 ml of butanol. After adding 10 ml of concentrated hydrochloric acid as a catalyst, esterification was carried out for 21/2 hours while removing water. 156 g of 80% hydrazine hydrate (2.5 mol) were added dropwise to the reaction solution, which had been cooled to 40 ° C., the mixture was boiled under reflux for one hour and cooled to about 70 ° C. 150 ml of concentrated hydrochloric acid and 150 ml of water were then added over the course of 15 minutes and the butanol was distilled off completely. The distillate removed was continuously replaced by water. The resulting crystal slurry was filtered, washed with water and dried.

Yield: 159.5 g of 3-phenylpyridazone- (6), which is 93% of theory.

Example 10

88 g (0.5 mol) of benzoylacrylic acid were dissolved in 200 ml of n-oc-tanol and 200 ml of toluene and, after the addition of 5 ml of concentrated hydrochloric acid as the catalyst, were esterified for 2 hours at the boiling point. 11 ml of water were removed. After the solution had been cooled to 70 ° C., 150 g of 50% hydrazine hydrate (1.5 mol) were added and the mixture was boiled under reflux for 3 hours with the removal of water. 400 ml of 9% hydrochloric acid were added to the reaction solution, and 100 ml of water and 240 ml of organic phase were distilled off within 1V2 hours. The reaction mixture was cooled and the crystals were filtered, washed on a suction filter with water and petroleum ether and dried.

Yield: 70.5 g of 3-penylpyridazone- (6), that is 82% of theory.

Example 11

106 g of methyl 3- (3'-nitro-4'-methoxybenzoyl) acrylic acid (0.40 mol) with mp: 153-154.4 ° C., prepared by esterification in the presence of p-toluenesulfonic acid according to Example 8 added in portions to a solution of 80 g hydrazine hydrate (1.6 mol) in methanol (600 ml). When heated to about 40 ° C, a brown solution was formed which was brought to reflux temperature for a further two hours. The mixture was then concentrated, cooled well, the solid product obtained was isolated and the latter was washed with water. This intermediate was suspended in water (325 ml) with stirring, hydrochloric acid was added (conc. 175 ml) and brought to reflux temperature for one hour. The reaction mixture was cooled and the resulting orange solid product was isolated, washed and dried. 76 g = 0.31 mol (77% of theory) of 3- (3'-nitro-4'-methoxy-phenyl) -pyridazone-6, which showed an mp of 277-280 ° C. recrystallized from dioxane.

f. C11H9NO4

calc .: C 53.44 H 3.67 N 17.00%

found: C 53.1 H 3.8 N 17.1%

The 3- (3'-nitro-4'-meth-oxybenzoyl) acrylic acid required for the feed ester was obtained by nitrating 3- (p-methoxybenzoyl) acrylic acid.

Example 12

582 g of p-fluorobenzoylacrylic acid with mp 134-137 ° C, (3 mol) were dissolved in ethanol (anhydrous 3.3 l) and with the addition of p-toluenesulfonic acid (23 g) and 4 ml of conc. Sulfuric acid refluxed under anhydrous conditions for 18 hours.

The mineral acid was blunted by adding anhydrous sodium bicarbonate and the inorganic salts were filtered off. 6 moles of hydrazine (dissolved in 700 ml of water) were added dropwise to the alcoholic solution of the esterification product and the mixture was heated under reflux for three hours. The separated product was isolated, washed with water and suspended in water. At 40 ° C, 700 ml of conc. Dropped in hydrochloric acid. After heating to reflux temperature for 2 hours, the precipitated 3- (p-fluorophenyl) pyridazone-6 was isolated, washed with water and dried. 390 g (2.05 mol), 68% of theory were obtained). It is a yellowish solid product with mp: 266-269 ° C.

f. C10H7FN2O

calc .: C63.16 H3.71 N 14.73%

found: C 63.2 H 3.8 N 14.8%

An almost colorless product was obtained by recrystallization from dioxane, which sublimed into broad crystals from about 170 ° C. and melted at 269-270.5 ° C.

Example 13

400 g of 3- (m-nitrobenzoyl) acrylic acid (1.8 mol) were esterified by boiling under reflux in methanol (4.2 l) for 18 hours with the addition of p-toluenesulfonic acid (30 g). The mixture was concentrated (2 l of distillate), hydrazine hydrate (300 ml, 6 mol) was added dropwise with thorough stirring and the reaction mixture was refluxed for three hours. With continuous addition of water (3 1), the methanol was distilled off, concentrated hydrochloric acid (1.2 1) was added and the mixture was boiled for a further three hours. After cooling, the crystals are isolated, washed and dried. The resulting beige, microcrystalline solid product, 286 g (corresponding to 73% of theory) 3- (m-nitrophenyl) pyridazon-6 (mp

269-274 ° C) melts after recrystallization from dioxane at 277-280 ° C.

f. C10H7N3O3

calc .: C 55.30 H 3.25 N 19.35 0 22.10%

found: C 54.6 H 3.5 N 19.2 O 22.9%

Example 14

40 g of methyl 3- (3'-nitro-4'-chlorobenzoyl) acrylic acid, mp: 139-142 ° C., prepared according to Example 8, were added in portions to hydrazine hydrate (33 g) in methanol (160 ml) and for two hours long cooked under reflux. It was concentrated in vacuo, cooled, the solid product obtained was isolated and washed with water. The suspension of this solid product in water (100 ml) was concentrated with stirring. Hydrochloric acid (50 ml) added and refluxed for two hours. The reaction mixture was cooled and the resulting 3- (3'-nitro-4'-chlorophenyl) pyridazone-6 was isolated, washed and dried. Yield 26 g, that is 69% of theory. Dissolved from dimethylformamide, it melts

270-272 ° C.

f. CI0H6CIN3O3

calc .: C 47.73 H 2.40 N 16.70 Cl 14.09%

found: C 48.2 H 2.7 N 16.3 Cl 14.1%

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The 3- (3'-nitro-4'-chlorobenzoyl) acrylic acid required for this experiment was obtained, for example, by nitrating 3- (p-chlorobenzoyl) acrylic acid.

Example 15

1400 g of 3- (2 ', 4'-dichlorobenzoyl) acrylic acid (5.7 mol) were esterified with ethanol (71) with the addition of p-toluenesulfonic acid (35 g) and concentrated sulfuric acid (10 ml) for 10 hours , wherein the water formed was distilled off by gasoline continuously. After removing the solvent in vacuo, the esterification product is added to a vigorously stirred solution of hydrazine hydrate (1.2 1, 24 mol) in water (3.51) within 20 minutes at 60 ° C. The mixture is kept at 95 ° C. for a further 3 hours, cooled and the product obtained is isolated and washed with water. For further reaction, the nutsche moist product was suspended in water with vigorous mechanical stirring, hydrochloric acid was added and the mixture was kept under gentle reflux for two hours. After cooling, the resulting product is isolated. The 3- (2 ', 4'-dichlorophenyl) pyridazone-6 obtained was washed with water and dilute sodium bicarbonate solution and dried. Yield 1094 g, with mp: 200-204 ° C, corresponding to a 79% yield, based on 3- (2 ', 4'-dichlorobenzoyl) acrylic acid.

f. C10H6Cl2N2O

calc .: C 49.83 H 2.50 N 11.62 Cl 29.42%

found: C 50.2 H 2.7 N 11.1 Cl 29.4%

Example 16

200 g of 3- (2 ', 4'-dimethylbenzoyl) acrylic acid were dissolved in methanol (2 l), p-toluenesulfonic acid (11 g) was added and the mixture was refluxed for 13 hours. After treatment with activated carbon, the methanol is removed in vacuo. This esterification product was added to a vigorously stirred hydrazine solution (1 1, 25%) and kept at 75-90 ° C. for one hour. After cooling, the solid product obtained was isolated and washed, suspended in water (700 ml) and concentrated hydrochloric acid (300 ml) was added to the reaction mixture. After heating to 90 ° C for one hour, the precipitated 3- (2 ', 4'-dimethylphenyl) pyridazone-6 was isolated, washed and dried.

Mp 138-141 ° C, yield 111g, that is 57% of theory.

f. C12H12NiO

calc .: C 71.98 H 6.04 N 13.99%

found: C 72.2 H 6.0 N 13.9%

Example 17

1025 g of 3- (2 ', 5'-dimethylbenzoyl) acrylic acid (5 mol) were esterified with ethanol (11) with the addition of concentrated sulfuric acid (6 ml), the water of reaction with benzene (41) being separated off by azeotropic distillation. The reaction solution was treated with activated carbon and the solvents were removed in vacuo. This esterification product was added to an aqueous hydrazine solution (41, 25%) within 10 minutes and refluxed for a further two hours. After cooling, the intermediate was isolated and washed. It was suspended in water (61), concentrated hydrochloric acid (1.2 l) was added and the mixture was slowly heated to 95 ° C. on a water bath. After two hours, the resulting crystals were isolated, washed with water and dried. 664 g of 3- (2 ', 5'-methylphenyl) pyridazon-6 with mp:

176-179 ° C, corresponding to a yield of 66% of theory. Dissolved from ethanol, the substance melts at 182-184 ° C.

f. ci2h12n2o calc .: C 71.98 H 6.04 N 13.99%

found: C 71.8 H 6.3 N 14.0%

Example 18

1046 g of 3- (p-ethylbenzoyl) acrylic acid ethyl ester, prepared according to the instructions of the preceding examples, were added dropwise at 35 ° C. to a solution of hydrazine hydrate (1050 g) in water (3250 ml) within half an hour. The mixture was then stirred for a further 3 hours. The resulting solid product was isolated and washed with water. The filter-moist product was suspended in water (6 l), concentrated hydrochloric acid (1.61) was added and the mixture was refluxed for two hours. The resulting 3- (p-ethylphenyl) pyridazone-6 was isolated, washed with water and dried, yield 613 g with a melting point of 185-187 ° C., which is 68% of theory.

f. c12h12n2o calc .: C 71.98 H 6.04 N 13.99%

found: C 71.2 H 6.3 N 14.2%

In an analogous manner, 3- (p-t-butylphenyl) pyridazon-6 with mp: 218-224 ° C. was also obtained.

f. c14h16n2o calc .: C 73.65 H 7.07 N 12.27%

found: C 73.7 H 7.2 N 11.8%

Example 19

325 g of 3- (p-cyclohexylbenzoyl) acrylic acid were dissolved in benzene (1.5 l), concentrated sulfuric acid (3 ml)

was added and ethanol (250 g) was slowly added dropwise to the extent when the esterification water formed separated from the boiling solution by azeotropic distillation. The inorganic acid was blunted by adding solid sodium bicarbonate, the inorganic salts removed by filtration and the solvents removed in vacuo. The crude esterification product which remained was added to a solution of hydrazine hydrate (230 g) in ethanol (11) and stirred for a further 5 hours. The mixture was concentrated in vacuo, cooled, the resulting solid product isolated and washed with water. For further processing, it was suspended in water (1.3 l), brought to about 30 ° C., concentrated hydrochloric acid (370 ml) was added dropwise and the mixture was boiled under reflux for a further two hours. The 3- (p-cyclohexylphenyl) pyridazone-6 separates as a light yellow solid product and was isolated, washed and dried. Yield 255 g with mp: 229-234 ° C, that is 80% of theory. Single recrystallization from dioxane brought the melting point to 240-244 ° C.

f. c16h18n2o calc .: C 75.56 H 7.13 N 11.02%

found: C 74.6 H 7.2 N 10.7%

Example 20

30 g of methyl 3- (3'-nitro-4'-methylbenzoyl) -acrylic acid, mp: 81-83 ° C., prepared according to the preceding examples, were added in portions to a mechanically stirred solution of hydrazine hydrate (25 g) in methanol (150 ml).

The mixture was refluxed for two hours. It was concentrated in vacuo, cooled well, the resulting solid product was isolated and washed with water. The nutsche moist product was suspended in water (100 ml), concentrated hydrochloric acid (60 ml) was added and the mixture was boiled under reflux for 1.5 hours. The reaction mixture was cooled and the resulting 3- (3'-nitro-4'-methylphenyl) pyridazone-6 was isolated, washed with water and dried. Yield 18 g with mp: 266-269 ° C, that is 65% of theory.

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f. c "h9n3o3

fro .: C 57.14 H 3.93 N 18.17 0 20.76%

found: C 56.7 H 3.6 N 18.4 0 21.2%

The 3- (3'-nitro-4'-methyl-benzoyl) acrylic acid required as starting material was obtained, for example, by nitrating 5 3- (4'-methylbenzoyl) acrylic acid (mp: 141-144 ° C.), f. CnH9N05

calc .: C 56.17 H 3.86 N 5.96%

found: C 56.6 H 3.9 N 6.0%

From this, the methyl ester of 3- (3'-nitro-4'-methylbenzoyl) acrylic acid used, with mp 81-83 ° C., is obtained by esterification with methanol and 10 p-toluenesulfonic acid.

Example 21

7 g of methyl 3- (m-nitrobenzoyl) acrylic acid (mp 15

107-109 ° C) was dissolved in ethanol (120 ml), 1.5 g of Pd carbon (containing 5.4% Pd) was added, and hydrazine hydrate (35 ml) was added dropwise with stirring. After refluxing for five hours, the catalyst was filtered off, the residue was extracted with ethanol and the solvent was largely removed in vacuo. The residue was suspended in water (80 ml), concentrated hydrochloric acid (20 ml) was added and the resulting solution was refluxed for one hour. The solution was then concentrated in vacuo until the first crystals began to separate, which were brought back into solution by adding water. The solution was brought to pH 7 with 5% sodium bicarbonate solution, concentrated to half the volume in vacuo, the resulting solid was isolated, washed with water and made from 50% aqueous 30

Recrystallized ethanol. The 6- (m-aminophenyl) pyridazone-6 obtained (yield 2.9 g, corresponding to 52% of theory) showed mp 206-208 ° C.

f. C10H9N3O

calc .: C 64.14 H 4.84 N 22.45%

found: C 64.3 H 4.9 N 22.7%

Example 22

255 g of 3- (p-bromobenzoyl) acrylic acid were suspended in 3 l of methanol and 25 g of p-toluenesulfonic acid were added. The mixture was refluxed for 40 hours. Methanol (1.5 l) was distilled off, hydrazine hydrate (250 ml) was added dropwise within 20 minutes and the mixture was brought to reflux temperature for 7 hours. The reaction solution separated out a solid product.

The methanol was removed by distillation, the reaction volume being kept constant by uniform addition of water (3 1), further water (2 1) and then concentrated hydrochloric acid (11) were added and the reaction was brought to reflux temperature for five hours. The reaction mixture was cooled and the resulting 3- (p-bromophenyl) pyridazone-6 was isolated, washed with water and dried. Yield 232 g (92% of theory), which start to sinter at 238 ° C and melt at 250 ° C.

f. C10H7BrN2O

calc .: C47.83 H2.81 N 11.16 B 31.83%

found: C 47.8 H 2.9 N 11.0 B31.5%

Dissolved from methanol, the compound melts at 251-253 ° C.

Claims (4)

621 543 2. The method according to claim 1, characterized in that the ester of formula II is reacted with at least 1.5 moles of hydrazine per mole of compound of formula II. 2nd PATENT CLAIMS 1. Process for the preparation of 3-pehyl-pyridazone- (6) of the formula = 0, (I) in which R and R ', which may be the same or different, are a hydrogen atom, an alkyl radical having up to 5 carbon atoms, a cycloalkyl radical, a halogen atom, a nitro group, a hydroxyl group, an O-alkyl group with 1 to 4 C atoms, an OCF3 group, a phenoxy group, an -S-CH3 group, an amino group or R and R 'together mean an alkylene grouping with 4 C atoms, characterized that you have an ester of 3-benzoyl-acrylic acid of the formula —CO — CH = CH — COOX, (II) This is because the yield obtained is only 16% and the desired product is heavily contaminated by other compounds (J. Chem. Soc. 1965, page 3347). After S. Gabriel u. J. Coiman - Ber. 32, Sèite 396, the conversion of benzoylacrylic acid and hydrazine to 3-phenylpyridazone- (6) does not succeed; on the other hand, the hydrazone of the acid used is formed. It has now been found that 3-phenylpyridazone- (6) of the formula 10th 15 in which X represents an alkyl radical with 1-8 C atoms, reacted with more than 1 mol of hydrazine per mol of compound of the formula II and the resulting reaction mixture or the isolated intermediate product is subjected to an acid treatment at elevated temperature. 3. The method according to claim 1, characterized in that the ester of formula II is reacted with 2-4 moles of hydrazine per mole of compound of formula II. 4. The method according to claim 1, characterized in that the intermediate product of the reaction with hydrazine is isolated before the acid treatment.