DE2213010A1 - 2-alkyl-2,3-dihydro-6-pyridazones - useful as pharmaceuticals and inters - Google Patents

Abstract

2-Alkyl-2,3-dihydro-6-pyridazones of formula (I): (where R1, R2 and R3 are halogen, H, an aliphatic residue, or the group -OR6, -SR6 or -NR6R7 (in which R6 and R7 are aliphatic, cycloaliphatic, araliphatic or aromatic residues or are linked so as to form a heterocyclic residue); R1 can also be SH, OH, NH2, -NHR6, a cycloaliphatic residue, an aromatic residue, CN, -NH-N(R8)2 (in which each R8 (same or different) is H or an aliphatic or aromatic residue) or -NH-SO2-R9 (in which R9 is an aromatic residue or is o-, m- or p-acetamidophenyl); R2 can also be OH, NH2, or -NH-R6; or R2 and R3 can be linked so as to form a ring; R4 is alkyl; and R5 is an aliphatic, cycloaliphatic, araliphatic or aromatic residue). (I) are pharmaceuticals (some compounds having effects on the central nervous system and some being active against pathogenic fungi and bacteria) and intermediates for pharmaceuticals, dyes and pesticides.

Description

Process for the preparation of 2-alkyl-2,3-dihydropyridazones- (6) Die The invention relates to a process for the preparation of 2-alkyl-2,3-dihydro-pyridazonen- (6) by reacting 2-alkyl-pyridazonium compounds with a nucleophilic reagent.

It has been found that 2-alkyl-2,3-dihydropyridazone- (6) of the general formula in which R1, R2 and R3 know to be the same or different and in each case a halogen atom, a hydrogen atom, an aliatic radical, the radical -OR6, the radical -SR6, the radical in which the individual radicals R6 and R7 can be identical or different and each denotes an aliphatic, cycloaliphatic, araliphatic, aromatic radical, or R6 and R7 together with the adjacent nitrogen atom also represent members of a heterocyclic ring, and R1 also denote the mercapto group, the hydroxyl group, the amino group, the rest wherein R6 has the aforementioned meaning, a cycloaliphatic radical, an aromatic radical, a cyano group, the radical in which the individual radicals R8 can be identical or different and each denotes a hydrogen atom, an aliphatic radical or an aromatic radical, the radical -NH-SO2-Rg, in which R9 an aromatic radical or the radical denotes, can stand, R2 also a hydroxyl group, an Auinogruppo or the remainder where R6 has the aforementioned meaning, R2 and R3 together with the carbon atoms adjacent to them can also mean members of a ring, R4 denotes an alkyl group, R5 stands for an aliphatic, cycloaliphatic, araliphatic or aromatic radical, advantageously obtained when 2 -Alkylpyridazonium compounds of the general formula in which R2, R3, R4 and R5 have the abovementioned meaning and Y denotes a Säur.anion, with a nucleophilic reagent of the general formula R1 Z III, in which R1 has the abovementioned meaning and Z denotes the cationic residue of a nucleophilic reagent a pH of at least 6.5.

If 1-phenyl-2-methyl-4-amino-5-chloropyridazonium methosulfate and malononitrile are used, the reaction can be represented by the following formulas: The process according to the invention provides a large number of the new 2-alkyl-2,3-dihydropyridazone- (6) in a simple and economical way in good yield and purity. 3. by reacting pyridazone- (6) with an alkylating agent according to the process described in DOS 1 913 265. Preferred starting materials II and III and correspondingly preferred end products I are those in whose formulas R1, R2 and R3 can be the same or different and in each case a chlorine atom, a bromine atom, a hydrogen atom, an alkyl radical with 1 to 6 carbon atoms, the radical -OR6 , the rest the rest -SR6, in which the individual radicals R6 and R7 can be identical or different and each denote an alkyl radical with 1 to 18, in particular 1 to 7 carbon atoms, a cyclohexyl radical, an aralkyl radical with 7 to 10 carbon atoms or a phenyl radical, or R6 and R7 together with the adjacent one Nitrogen atom also stands for members of a 5- or 6-membered heterocyclic ring, which in addition to the nitrogen atom can also contain an oxygen atom or another nitrogen atom, and R also denotes the mercapto group, the hydroxyl group, the amino group, the remainder wherein R6 has the aforementioned meaning, the remainder a cycloalkyl radical with 5 or 6 carbon atoms, which can optionally also contain 1 or 2 double bonds or 1 or 2 oxo groups, a phenyl radical, a cyano group, the radical in which the individual radicals R8 can be identical or different and each represent a hydrogen atom, an alkyl radical with 1 to 4 carbon atoms or a phenyl radical, the radical -NH-802-R91 in which R9 is a phenyl radical or N-acetylanilino radical, in particular pN-acetylanilino radical , designated. can stand, Ro also the hydroxyl group, the amino group, the remainder where R6 has the aforementioned meaning, R2 and, together with the carbon atoms adjacent to them, members of a 5- or 6-membered ring which, in addition to carbon atoms, also have 1 or 2 nitrogen atoms or 1 oxygen atom and / or 1 or 2 further double bonds can contain, mean, R5 stands for an alkyl radical with 1 to 12 carbon atoms, a cycloalkyl radical with 5 to 8 carbon atoms, an aralkyl radical with 7 to 10 carbon atoms or a phenyl radical, In the preferred starting materials, R4 denotes an alkyl group with 1 to 3 carbon atoms and Y is a chlorine atom, bromine atom, iodine atom, perchlorate, sulfate, phosphate, nitrate, tetrafluoroborate, chlorate, the radical OS02R10, in which R10 is an aromatic radical, in particular phenyl or tolyl radical, the radical wherein R4 has the aforementioned preferred meaning, or the anion of an alkane, cycloalkane, aralkanecarboxylic acid such as formate, acetate, benzoate, cyclohexylcarboxylate. The radicals mentioned can also be replaced by groups and / or atoms which are inert under the reaction conditions, e.g. chlorine atoms, bromine atoms, fluorine atoms, nitro groups, cyano groups, carbonamido groups, alkoxy groups with 1 to 4 carbon atoms, carbalkoxy groups with 2 to 6 carbon atoms, alkyl groups with 1 to 4 carbon atoms, Trifluoromethyl groups.

For example, the following 2-alkyl-pyridazonium compounds can be used as starting materials II can be used: 1-methyl-2-methyl-4-amino-5-chloropyridazonium methosulfate, 1-methyl-2-methyl-4-anilino-5-bromopyridazonium perchlorate, 1-isopropyl-2-methyl-4-amino-5-chloropyridazonium methosulfate, 1-Benzyl-2-methyl-4-amino-5-chloropyridazonium perchlorate, 1-phenyl-2-ethyl-4-chloro-5-phenoxypyridazonium tetrafluoroborate, 1-Cyclohexyl-2-methyl-4-amino-5-chloropyridazonium perchlorate, 1-phenyl-2-methyl-4-amino-5-chloropyridazonium perchlorate, 1-phenyl-2-methyl-4-amino-5-chloropyridazonium chloride, 1-phenyl-2-methyl-4-amino-5-bromo-pyridazonium tosylate, 1-phenyl-2-methyl-4-diethylamino-5-bromopyridazonium perchlorate, 1-phenyl-2-methyl-4-pyrrolidino-5-bromopyridazonium perchlorate, 1-phenyl-2-methyl-5-N-methyl-N-benzylaminopyridazonium perchlorate, 1-phenyl-2-methyl-5-N-methyl-N-cyclohexylaminopyridazonium perchlorate, 1-phenyl-2-methyl-4-hydroxy-5-methoxy-pyridazonium perchlorate, 1-phenyl-2-methyl-4-methoxy-5-bromo-pyridazonium perchlorate, 1-phenyl-2-methyl-4-methyl-pyridazonium perchlorate, 1-phenyl-2-methyl-4-chloropyridazonium perchlorate, 1-phenyl-2-methyl-4-methylthio-oxy-pyridazonium perchlorate, 1-phenyl-2-methyl-5-cyclohexyl-oxy-pyridazonium perchlorate, 1-phenyl-2-methyl-5-phenylthio-pyridazonium perchlorate, 1-phenyl-2-methyl-4,5-benzopyridazonium perchlorate, 1-phenyl-2-ethyl-4-amino-5-chloropyridazonium ethosulfate, 1-p-tolyl-2-methyl-4-amino-5-chloropyridazonium perchlorate, 1-o-chloro-phenyl-2-methyl-4-amino-5-chloro-pyridazonium perchlorate, 1-m-trfluoromethyl-phenyl-2-methyl-4-amino-5-chloro-pyridazonium perchlorate and the corresponding in the 4- and / or 5-position by a cyclohexylthio group, Phenoxy group, benzoxy group, benzyl-thio-group, N-ethyl-anilino-group, N-piperidino-group, N-morpholino group-substituted 1-phenyl-2-methyl-pyridazonium perchlorate; analog chlorides, bromides, iodides, sulfates, acetates, formates, borates, chlorates, phenylsulfonates, Tolyl sulfonates, tetrafluoroborates.

Nucleophilic reagents are understood here to mean those substances those in a polar reaction, such as s [Bo the reaction according to the invention, at least have a pair of electrons distributed asymmetrically and so from a nucleophilic part and consist of a cationoid (electrophilic) residual part. As a nucleophilic part (nucleophile), which may be present in the form of nucleophilic ions during the reaction can, those residues or particles are designated which have free electron pairs @@@ have a Ke @@ in the method according to the invention, the 3-position of the Hy @ @@@@ (6) -kernes, search.

The inventive Ver @@@ rer @@@ @@@@ a polar or

ionic and nucleoph @@@ @ eakti @@, as the active reagent in the starting material III a Ku @@@ op @@ @ Regarding the definition of the mentioned subject @ us @ @@ and @@@ meaning is on Ullmanns Encyklop @ die d @@ @ ec @@ Chemie, Volume 14, Pages 585 and 586 and @@@ d @ h @@ @try @@ @ @ Compounds (Elsevier Publ. Co., N.Y. @@ 31, @ 1, 63, 164, and Volume IIIA (1954), page @ @@ wi @@, d @@ at the same time also the better known Nucleophil @ @ nf @@ @ @@@ @@ gte Nucleophiles are those of the general @@ mel @ mentioned above @ bodent t @@@@ ug @ has a preferred meaning of a hydrogen atom or a metal the @@@ of the implementation form the proton or metal cation, each of which d @ s @@@ rea @@ @@@ bind starting material II.

For example, Z denotes a metal @m and accordingly R1 the to Z ge @@ nde @ e nucleophile of the nucleophilic reagent in the following starting materials III, alkali hydroxides such as sodium hydroxide; Alkali and Er @ alkali salts Potassium cyanide; Metal alkyls such as lithium ethyl, metal @@@ an such as sodium hydride; Alkanolates, cycloalkanolates, Aralk @aten, phenolates such as lithium benzylate, Kal @ nmoyclohexanolat, calcium phenolate, Aluminum isopropylate, magnesium methylate, mercaptides such as potassium ethyl mercaptide. Z denotes e.g. hydrogen bonded to the heteroatom in aromatic, cycloal @ @atic, araliphatic alcohols such as phenol, pentachorphenol, benzyl alcohol, Cyclohexanol, corresponding M @ re @ pors such as methyl mercaptan, benzyl mercaptan, 2-diethylamine-ethyl-mercaptan-hydrochloride, Dodecyl mercaptan, thiophenol, and Thi @@ carbazid, where R1 is the isothiosemicarbazide nucleophile reacts by means of the mercapto group; corresponding primary and secondary amines, where the hydrogen atom Z sits on the nitrogen atom. Like methylamine, 2-phenylpropylamine- (1), m-trifluoromethylaniline, 2-methylhexamethyleneimine, laurylamine. Srearylamine, dimethylamine, Aniline, morpholine, piperidine, pyrrolidine, and hydrazines such as phenylhydrazine, N, N-dimethylhydrazine; Sulphamides such as toluenesulphamide, p-acetylsulphanilic acid amide. Substances, which the starting material III or the nucleophile R1- and the cationoid part Z- during of the reaction, e.g. lithium aluminum hydride, sodium borohydride in an aqueous medium, where Z is a metal cation and R1 $ a, or sodium bicarbonate, where Z denotes sodium cation and R1 denotes hydroxyl anion. Z can also be a cationoid Adduct, e.g. 0 gBr + in ethylmagnesium bromide or phenylmagnesium bromide, the is further converted in the reaction and finally in the form of that contained in the adduct Metal, e.g. magnesium, which binds acid anion Y. Z can also be hydrogen of CH-acidic compounds, with CH-acidic compounds being those that easily split off the hydrogen bound to carbon in the form of protons, be understood. Such CH-acidic compounds are e.g. nitromethane, cyanoacetic acid ester, Cyanoacetic acid nitrile, cyanoacetic acid amide, malonic acid esters such as the diethyl ester, Acetoacetic ester, cyclopentadiene. In these cases a proton splits on one C-H bond acidified by substituents, e.g. at the 2-position of Dimedon (5,5-dimethylcyclohexane-1,3-dione), or on the CH2 member of the cyclopentadiene. Likewise are the CH-acidic compounds whose easily removable hydrogen atom is through a metal atom is replaced, e.g. sodium malonic acid ester, is suitable; Z then means the metal atom.

The starting materials III are used in a stoichiometric amount, based on on starting material II, or in excess, e.g. in an up to 3-fold excess. The reaction is usually carried out at a temperature between 0 and 1000C, preferably between 10 and 500C, without pressure or under pressure, continuously or discontinuously carried out. It is advantageous to use water or in the reaction under the reaction conditions inert solvents, æ.B0 hydrocarbons such as ligroin, cyclohexane; aromatic Hydrocarbons such as benzene, xylene, nitrobenzene, chlorobenzene; Chlorinated hydrocarbons such as carbon tetrachloride; Ethers such as dioxane, tetrahydrofuran, diethyl ether; Ketones such as acetone, cyclohexanone; Nitriles such as acetonitrile; Esters such as ethyl acetate, Butyl acetate; or equivalent Mixture Implementation is at carried out at a pH of at least 6.5, preferably from 6.8 to 8.5. Because nucleophilic As a rule, reagents are bases, but this is often sufficient due to the starting material III adjusted pH in the reaction mixture. You can also use inorganic to adjust the pH or use organic bases, e.g. sodium hydroxide solution if water is used as the reaction medium Alkali, zinc and alkaline earth compounds such as hydroxides, oxides, Carbonates, bicarbonates or salts of weak or polybasic acids are used will.

There are e.g. possible bases: potassium hydroxide, sodium hydroxide, Potassium carbonate, sodium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, Calcium hydroxide, barium oxide, calcium carbonate, zinc oxide, sodium acetate, sodium propionate, ethylene glycolate, methylate, ethylate, tripropylene glycolate, trimethylamine, triethylamine, Pyridine, diethylaniline, dimethylaminoethanol, N-ethylpiperidine, N-methylpyrrolidinO In organic solvents, with the addition of inert bases, e.g.

tertiary bases such as triethylamine, or in the case of implementation with Amines with an excess of amine or in the reaction with organomagnesium Compounds work without the addition of base.

The reaction can be carried out as follows: The starting material II, optionally together with the solvent, is mixed thoroughly the starting material III is added at the reaction temperature. The mixture will then held at the reaction temperature for a further 0.1 to 10 hours. Then the End product from the mixture in a known manner, for example by filtration; by evaporation of the mixture, treating the residue with one of the aforementioned solvents and filtration; Extraction with a suitable solvent, e.g. benzene, and Removal of the solvent, separated.

The novel compounds which can be prepared by the process of the invention are pharmaceuticals and valuable raw materials for the manufacture of dyes, Pharmaceutica and pesticides. They are, in part, effective means to influence the central nervous system, against pathogenic fungi and against pathogens Bacteria. For example, the end product mentioned in Example 9 already shows one concentration from 1: 10,000 good effect against Staphylococus aureus, against Streptococus fecal and against the fungal spaces Trichophyton mentagrophytes, Trichophyton rubrum and Epidermophyton flocosum. Examples 4 and 17 show further uses.

The parts listed in the following examples are parts by weight.

Example 1 28.65 parts of 1-phenyl-2-methyl-pyridazonium perchlorate are in 250 parts of water with stirring at 20 to 40 ° C with 20 parts of sodium bicarbonate offset. After 30 minutes, 18.3 parts (89.7% of theory) 1-phenyl-2-methyl-3-hydroxy-2,3-dihydropyridazone (6) away; M.p .: 105-107 ° C.

Example 2 Analogously to Example 1, 1-phenyl-2,4-dimethyl-pyridazonium perchlorate is obtained from 30 parts 16 parts (73.4% of theory) 1-phenyl-2,4-dimethyl-3-hydroxy-2,3-dihydro-pyridazon- (6) with a m.p .: 130 to 131 ° C (dec.).

Example 3 Analogously to Example 1, 1-phenyl-2-methyl-4-chloropyridazonium perchlorate is obtained from 32.1 parts 17.3 parts (72.3% of theory) 1-phenyl-2-methyl-3-hydroxy-2,3-dihydro-4-chloropyridazon- (6); Mp. (From ethyl acetate) 110 to 11200.

Example 4 Analogously to Example 1, 1-phenyl-2-methyl-4-methoxy-5-bromopyridazonium perchlorate is obtained from 39.55 parts 26.5 parts (85% of theory) 1-phenyl-2-methyl-3-hydroxy-2,3-dihydro-4-methoxy-5-bromo-pyridazon- (6); Mp (from acetonitrile) 15700 (with decomposition). The end product is involved in solutions 01% by weight of active ingredient against cotton bugs.

Example 5 Analogously to Example 1, 1-phenyl-2-methyl-4-diethylamino-5-chloropyridazonium perchlorate is obtained from 39.2 parts 28 parts (90.6% of theory) 1-phenyl-2-methyl-3-hydroxy-2,3-dihydro-4-diethyl-amino-5-chloro-pyridazon- (6); M.p .: 155 to 156 ° C. (from acetonitrile) Example 6 17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloropyridazonium methosulfate are dissolved in 258 parts of water and at 30 ° C with stirring with 5 parts of sodium borohydride offset. After one hour, 11 parts (92.8% of theory 1-phenyl-2-methyl-2,3-dihydro-4-amino-5-chloro-pyridazon- (6) away. Mp. (From methanol) 164 ° C. (with decomposition).

Example 7 17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are dissolved in 250 parts of methanol at 600C with 6 parts of sodium methylate in 14 Parts of methanol are added. The reaction mixture is allowed to boil for a further 30 minutes and after cooling and filtering off with suction, 10 parts (74.8 ffi of theory) of 1-phenyl-2-methyl-3-methoxy-2,3-dihydro-4-amino-5-chloropyride are obtained azon- (6); M.p .: 177-178 ° C (dec.).

Example 8 34.75 parts of 1-phenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are in 25Z parts of ethanol with 26.6 parts of pentachlorophenol and 10 Parts of triethylamine are added. The reaction mixture is heated to boiling for one hour, then the alcohol is evaporated and the remaining residue with 300 parts of water offset. After filtering off with suction and drying, 42 parts (83.8% of theory) are obtained 1-phenyl-2-methyl-3- (pentachlor) -phenoxy-2,3-dihydro-4-amino-5-chloro-pyridazon- (6); Mp. (From acetonitrile) 125 ° C. (with decomposition).

Example 9 Analogously to Example 8, pentachlorophenol is used instead of pentachlorophenol 11 parts of thiophenol and, as starting material II, 42 parts of 1 phenyl-2-methyl-4-amino-5-phenylthiopyridazonium methosulfate and receives 28 parts (66.7% of theory) 1-phenyl-2-methyl »3,5-di- (phenylthio) -2,3-dihydro-4-aminopyridazon- (6); M.p .: 180 to 1820C (from acetonitrile).

Example 10 17.4 parts of 1-rhenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are dissolved in 200 parts of water, with 8.5 parts of 2-diethylamino-ethyl-mercaptan hydrochloride added and diluted aqueous sodium hydroxide solution is added at 20 ° to 250 ° C. while stirring (10% by weight) added until a pH of 7.5 to 8 is reached. That which is formed in the process The reaction product is extracted with benzene. Obtained after evaporation of the benzene one 15.6 parts (84.7% of theory) 1-phenyl-2-methyl-3- (ß-diethyl-amino) -ethylthio-2,3-dihydro-4-amino-5-chloro-pyridazon- ( 6).

M.p. (from benzene-cyclohexane) 108 to 11,000.

Example 11 17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are dissolved in 250 parts of water, mixed with 4.5 parts of thiosemicarbazide and while stirring at 400C, 20 parts of dilute sodium hydroxide solution (10 percent by weight) adjusted to a pH of 8. 9.5 parts (58.2 k of theory) of 1-phenyl-2-methyl-3-isothiosemicarbazido- (S) -2.3 are obtained dihydro-4-amino-5-chloropyridazon- (6) of m.p. (from acetonitrile) 162 to 1640C (dec.).

Example 12 19.6 parts of 1-phenyl-2-methyl-4-amino-5-bromopyridazonium methosulfate, 200 parts of ethanol, 20 parts of dodecyl mercaptan, 10 parts of triethylamine are under heated to reflux for one hour with thorough mixing. By adding water and Filtration of the mixture gives 18 parts (73.2% of theory) of 1-phenyl-2-methyl-3-dodecylthio-2,3-dihydro-4-amino-5-bromopyridazone- (6); M.p. (from methanol) 117 to 11900.

Example 13 17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are dissolved in 200 parts of water and stirring at 3500 with a solution that consists of 3.5 parts of potassium cyanide in 30 parts of water, is obtained after Filtration 11.5 parts (87.7 s of theory) 1-phenyl-2-methyl-3-cyano-2,3-dihydro-4-amino-5-chloropyridazon- (6) of fp .: 15800 (dec.).

Example 14 2.4 parts of magnesium are in the form of the Grignard reaction 11 parts of ethyl bromide are added in 50 parts of diethyl ether and the mixture is so kept boiling for a long time until a clear solution is present. Then you give a suspension of 17.4 parts of 1-PhenFl-2-methyl-4-amino-5-chloropyridazonium methosulfate in 100 parts of diethyl ether and heated at 3400 for one hour.

The reaction mixture is diluted with 300 parts of hydrochloric acid (10 % By weight) and the end product formed is sucked off.

4 parts (30.1 ffi of theory) of 1-phenyl-2-methyl-3-ethyl-2,3-dihydro-4-amino-5-chloro-pyridazon- (6) are obtained; Mp (from acetonitrile) 190 to 191 ° C (decomp.).

Example 15 As in Example 14, the ethyl bromide is used instead 16 parts of bromobenzene and 14 parts (89.5% of theory) of 1,3-diphenyl-2-methyl-2,3-dihydro-4-amino-5-chloro-pyridazon- (6) Mp (from acetonitrile) 239 to 241 ° C (with decomposition).

Example 16.

17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloropyridazonium methosulfate are dissolved in 250 parts of water and 5 parts of nitromethane are added while stirring By adding dilute sodium hydroxide solution at 20 to 25 ° C, the reaction mixture Set strongly alkaline (pH 14) and sucked off. 10 parts are obtained as filter material (67.5% of theory) 1-phenyl = 2-methyl-3-nitromethyl-2,3-dihydro-4-amino-5-chloropyridazone (6); Mp (from acetonitrile) 213-21500 (dec.).

Example 17 17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are dissolved in 250 parts of water and with stirring with a solution consisting from 3.5 parts of malononitrile and 30 parts of dioxane, added. At 20 to 250C it will A pH of 7.0 was set with dilute sodium hydroxide solution (10% by weight). Receives 14.8 parts (98.4% of theory) of 1-phenyl-2-methyl-3- (dicyano) -methyl-2,3-dihydro-4-amino-5-chloropyridazon- (6); Mp (from water-methanol) 171 to 172 ° C (decomp.). The end product works in solutions with 0.1% by weight active ingredient against nematodes.

Example 18 Analogously to Example 17, malononitrile is used instead of the malononitrile 7 parts of acetoacetic ester and 9.4 parts (51.5% of theory) of 1-phenyl-2-methyl-3-α- (carbethoxy) -acetonyl-2,3-dihydro-4-amino-5-chloropyridazone are obtained - (6); Mp (from acetonitrile) 127-13000 (dec.).

Example 19 18 parts of 1-phenyl-2-methyl-4,5-dimethoxypyridazonium methosulfate are dissolved in 150 ml parts of water and with stirring at 25 ° C with 5 parts of cyanoacetamide offset. A pH value of 8 is set by adding dilute sodium hydroxide solution after filtration, 10.6 parts (64.3 oZ of theory) 1-phenyl-2-methyl-3- (α-cyano) -acetamido- (α) -methyl-2,3-dihydro-4 are obtained, 5-di methoxy-pyridazon- (6); Fpo 158 to 1590C (from acetonitrile) Example 20 Analogous to the example 17, 19.7 parts of 1,2-dimethyl-4-anilino-5-bromopyridazonium perchlorate are used and receives 13.7 parts (76.2% of theory) 1,2-dimethyl-3- (dicyano) -methyl-2,3-dihydro-4-anilino-5-bromo-pyridazon- (6); M.p .: 138-140 ° C.

Example 21 As in Example 17, 17.2 parts of 1-phenyl-2-methyl-4-hydroxy-5-methoxypyridazonium methosulfate are used and when working up with dilute sodium hydroxide solution, it has a pH of 6.8 up to 7 a £ 6.5 parts (43.7% of theory) of 1-phenyl-2-methyl-3- (dicyano) -methyl-2,3-dihydro-4-hydroxy-5-methoxypyridazone are obtained (6); M.p .: 120 to 1230C (dec.).

Example 22 17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are dissolved in 200 parts of water and with stirring at 20 to 250 parts with 7 parts 2-phenyl-propyl-amine- (1) added.

A pH of 8 is set with dilute sodium hydroxide solution. You get 17 parts (91.9% of theory) 1-phenyl-2-methyl-3- (22-phenyl) -n-propylamino-2,3-dihydro-4-amino-5-chloropyridazon- (6); M.p .: 135-13700 (from acetonitrile).

Example 23 17.4 parts of 1-phenyl-2-methyl-4-amino-5-chloro-pyridazonium methosulfate are dissolved in 250 parts of water, with 50 parts of a hydrochloric acid solution, the 5 Contains parts of aniline, added and diluted at -5 ° C to OOC with stirring Sodium hydroxide solution made alkaline (pH 14). After filtration, 11 parts (67 % of theory) 1-phenyl-2-methyl-3-anilino-2,3-dihydro-4-amino-5 chloropyrldazon- (6); M.p .: 170 to 172 ° C (dec.).

If the reaction is carried out at a temperature of 80.degree. C., then 13 parts (79.2 ffi of theory) of the end product.

Example 24 18 parts of 1-phenyl-2-methyl-2-4,5-dimethoxypyridazonium methosulfate are dissolved in 150 parts of water, with 20 parts of 10 percent strength by weight hydrochloric acid and 4.5 parts of morpholine were added.

The mixture is stirred at 2000 with dilute sodium hydroxide solution adjusted to pH 14. After filtration, 12 parts (72.1% of theory) are obtained 1-phenyl-2-methyl-3-N-morpholinyl-2,3-dihydro-4,5-dimethoxypyridazon- (6); Fp .: 118 to 120 ° C (from cyclohexane3.

Example 25 19.6 parts of 1-phenyl-2-methyl-4-amino-5-bromo-pyridazonium methosulfate are dissolved in 200 parts of water, with 20 parts of 10 percent hydrochloric acid and 8 Parts of m-trifluoromethyl aniline are added.

At 200 ° C., the mixture is adjusted to pH with sodium hydroxide solution while stirring 14 and after filtration receives 18 parts (82% of theory) 1-phenyl-2-methyl-3-m-trifluoromethyl-anilino-2,3-dihydro-4-amino-5-bromopyridazon- (6); M.p .: 171 ° C (from acetonitrile).

Example 26 Analogously to example 25, m-trifluoromethylaniline is used instead of m-trifluoromethylaniline 5.7 parts of 2-methyl-hexamethyleneimine and receives 15.3 parts (77.9% of theory) 1-phenyl-2-methyl-3- (2'-methyl) -hezcamethyleneimino-2,3-dihydro-4- amino-5-bromo-pyridazon- (6); M.p .: 117 to 119 ° C.

Example 27 5 parts of 1-phenyl-2-methyl-4,5-benzopyridazonium perchlorate are in 50 parts of methanol with 0.75 parts of sodium methylate for 10 minutes at 600C held. After cooling, the end product is filtered off with suction and is then washed with 50 parts of water 3.2 parts (87.5% of theory) 1-phenyl-2-methyl-3-methoxy-2,3-dihydro-4,5-benzopyridazon- (6); M.p .: 163 to 165 ° C.

Example 28 2 parts of 1-phenyl-2-ethyl-5-ethyl-thio-pyridazonium tetrafluoroborate are stirred in 50 parts of water with 2 parts of sodium bicarbonate for 2 hours at 300C. Analogously to Example 1, 1.1 parts (68.7 s of theory) of 1-phenyl-2-ethyl-3-hydroxy-2,3-dihydro-5-ethyl-thiopyridazone (6) are obtained; M.p .: 115 ° C (decomposition (from ethyl acetate).

Example 29 8.3 parts of 1-phenyl 2-ethyl-4-chloro-5-phenoxypyridazonium tetrafluoroborate are stirred in 50 parts of aqueous 10 percent strength by weight hydrochloric acid and with a Solution consisting of 50 parts of 10 percent strength by weight hydrochloric acid and 2 parts of aniline, offset.

10 percent strength by weight sodium hydroxide solution is added up to a pH of 7.5 to 7.8 and sucks off the end product formed. 6.2 parts (73.8 % of theory) 1-phenyl-2-ethyl-3-anilino-2,3-dihydro-4-chloro-phenoxy-pyridazon- (6); Fp .: 168 to 17000 (from acetonitrile)

Claims (2)

Process for the preparation of 2-alkyl-2,3-dihydropyridazonen- (6) of the general formula in which R1, R2 and R3 can be the same or different and each represents a halogen atom, a hydrogen atom, a. aliphatic remainder, the remainder -OR6, the remainder -SR6, the remainder wherein the individual radicals R6 and R7 can be the same or different and each denote an aliphatic, cycloaliphatic, araliphatic, aromatic radical, or R6 and R7 together with the adjacent nitrogen atom also represent members of a heterocyclic ring, in addition Rx also represent the Mercapto group, the hydroxyl group, the amino group, the rest wherein R6 has the aforementioned meaning, a cycloaliphatic radical, an aromatic radical, a cyano group, the radical in which the individual radicals R8 can be identical or different and each represent a hydrogen atom, an aliphatic radical or an aromatic radical, the radical -NH-SO2-R9, in which Rg an aromatic radical or the radical denotes, can stand, R2 also a hydroxyl group, an amino group, the remainder where R6 has the aforementioned meaning, R2 and R3 together with the carbon atoms adjacent to them can also denote members of a ring1 R4 denotes an alkyl group, R5 denotes an aliphatic, cycloaliphatic, araliphatic or aromatic radical, characterized in that 2 -Alkyl-pyridazonium compounds of the general formula in which R2, R3, R4 and R5 have the abovementioned meaning and Y denotes an acid anion, with a nucleophilic reagent of the general formula R1 - Z III, in which R1 has the abovementioned meaning and Z denotes the cationic residue of a nucleophilic reagent, at a pH of at least 6.5 converts. 2. 2-Alkyl-2,3-dihydropyri @@@ ne- (6) of the general formula in which R1, R2 and R3 can be identical or different and in each case a halogen atom is a hydrogen atom, an aliphatic radical, the radical -OR @ the radical -SR6, the radical in which the individual radicals R6 and R7 can be identical or different and each denote an aliphatic, cycloaliphatic, araliphatic, aromatic radical, or R6 and R7 together with the adjacent nitrogen atom also represent members of a @eterocyclic ring, in addition R1 also denote the mercapto group, the hydroxyl group, the amino group, the rest wherein R6 has the aforementioned meaning, a cycloaliphatic radical, an aromatic radical, a cyano group, the radical in which the individual radicals R8 can be identical or different and each represent a hydrogen atom, an aliphatic radical or an aromatic radical, the radical -NH-SO2-R9, in which R9 an aromatic radical or the radical denotes, can stand, R2 also a hydroxyl group, an amino group, the remainder wherein R6 has the aforementioned meaning, can denote R2 and R; together with the carbon atoms adjacent to them, they can denote members of a ring, R4 denotes an alkyl group, R5 denotes an aliphatic, cycloaliphatic, araliphatic or aromatic radical.