GB2052481A

GB2052481A - 4-Substituted 5,6,7,8- tetrahydroquinolines, their preparation and use

Info

Publication number: GB2052481A
Application number: GB8015365A
Authority: GB
Original assignee: Hoechst AG
Current assignee: Hoechst AG
Priority date: 1979-05-09
Filing date: 1980-05-09
Publication date: 1981-01-28
Also published as: DE2918591A1; GB2052481B

Abstract

The invention provides a compound of the general formula <IMAGE> in which R<1> and R<2> represents H or another substituent, or R<1> and R<2> together represent -CH2CH2CH2CH2-; R<3>, R<4>, R<5> and R<6> represent H or an alkyl group; and A represents a substituent linked to the tetrahydroquinoline ring by a nitrogen or sulphur atom. The compounds are effective against fungi; bacteria and algae.

Description

SPECIFICATION 4-Substituted 5,6,7,8-tetrahydroquinolines, their preparation and use The present invention relates to 5,6,7,8-tetrahydroquinolines substituted in the 4-position, the synthesis thereof and their use as fungicides, bactericides and algicides.

The present invention provides a compound of the general formula (I)

in which R1 represents a hydrogen atom, a straight chain or branched chain (C1-C12)alkyl radical, a benzyl or phenyl radical which may be unsubstituted or substituted by one or more of the same of different substituents selected from halogen atoms, trifluoromethyi radicals and (C1-C4)alkyl groups, a (C1-C6)alkoxycarbonyl radical, an arylaminocarbonyl radical wherein the aryl radical may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl radicals and (C144)alkyi groups, a N-alkyl-arylaminocarbonyl radical wherein the alkyl radical has from 1 to 3 carbon atoms and the aryl radical may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups and (C1-C4)alkyl groups, an aminocarbonyl radical, or a mono- or dialkylaminocarbonyl radical wherein the or each alkyl group has from 1 to 10 carbon atoms, R2 represents a hydrogen atom, a straight chain or branched chain (C1-C12)alkyl group, a halogen atom, a benzyl group or phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups, nitro groups and (C1-C4)alkyl groups, an alkoxycarbonyl radical wherein the alkyl group has from 1 to 6 carbon atoms, a phenylthio group, a morpholino group, a piperidino group, or an arylamino group the aryl group of which may be unsubstituted or substituted by one or more (C1-C4)alkyl groups or R' and R2 together represent -CH2CH2CH2CH2-, R3 represents a hydrogen atom or a (C1-C4)alkyl group, R4 represents a hydrogen atom or a straight chain or branched chain (C1-C12)alkyl group, R5 represents a hydrogen atom or a (C1-C4)alkyl group, R6 represents a hydrogen atom or a (C1-C6)alkyl group and A represents one of the following groups:

wherein n is 2 or 3 and R7.R6, Fle and Y and Y' have the following meanings: R7 represents a straight chain or branched chain (C1-C12)alkyl group, an arylalkyl group wherein the aryl moiety may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms and trifluoromethyl groups, a furylaky group, a hydroxyalkyl group, a radical of the formula -CH2COOH, -CH(CH3)COOH, -CH2CH2COOH,

a phenyl radical which may be unsubstituted or substituted by one or more of the same or different substituents selected from hydroxy groups, halogen atoms, nitro groups, (C1-C4)alkyl groups and -COOH groups, a naphthyl group, a cyclohexyl group, or a heterocyclic group containing one or more hetero atoms.

R8 represents a phenyl group which may be unsubstituted or substituted by one or more of the same or different substitutents selected from halogen atoms, trifluoromethyl groups, nitro groups, (C1-C4)alkylgroups, dimethylamino groups, -COOalkyl groups, alkoxy groups, phenoxy groups and halogen-substituted phenoxy groups, a benzamido group, a cycloalkyl group, a straight chain or branched chain alkyl group of the general formula

or -CH2CH2CH2R14.

wherein R10 to R14 have the following meanings: R10 represents a hydrogen atom, a furyl group, a piperidino group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, (C1-C4)alkyl groups, cyano groups, and dioxomethylene groups, a dialkylamino group wherein each alkyl group has from 1 to 5 carbon atoms, a piperidyl group, a morpholino group, a bicyclo-[2,2,1 ]-heptyl group or an unsubstituted or substituted cyclohexyl group, R11 represents a hydrogen atom or a (C1-C4)alkyl group, R12 represents a hydrogen atom or a (C,C4)alkyl group, R'3 represents a hydroxy group, a dialkylamino group having from 1 to 5 carbon atoms in each alkyl chain, an alkoxy group, a hydroxyalkylamino group, or an unsubstituted or substituted phenyl group, R'4 represents a dialkylamino group having from 1 to 5 carbon atoms in each alkyl chain, a (C1-C4)alkoxy group, a hydroxy group, a morpholino group, a N-alkylpiperazino group, an alkylamino group or a hydroxyalkylamino group, R9 represents a hydrogen atom, a straight chain or branched chain (C1-C6)alkyl group (when R8 represents a phenyl group), a hydroxyalkyl group or a benzyl group, or R8 and R9 together represent one of the following groups:: -N=CH-N=CH-, -CH2CH2OCH2CH2-, -CH2CH2CH2CH2-,

Y represents a C1-C18)alkyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from (C1-C3)alkyl groups, halogen atoms, trifluoromethyl groups and nitro groups which may be benzoannellated, or a (C5-C8)cycloalkyl group, and Y' represents a hydrogen atom or may also represent a (C1-C4)alkyl group when Y represents a (C1-C4)alkyl group.

In addition, R', R2, R7, R8, R9, R10, R13, R14 and Y may present an unsubstituted or substituted phenyl or aryl radical or an unsubstituted or substituted hererocyclic radical containing one or more hetero atoms. It is to be understood that all alkyl radicals mentioned above may be straight chain or branched chain radicals.

More especially the present invention provides a compound of the general formula (I')

in which R' represents a hydrogen atom, a straight chain linear or branched chain (C1-C12)alkyl group, a benzyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from one or two chlorine atoms, trifluoromethyl groups and (C1-C4)alkyl groups, a (C1-C6)alkoxycarbonyl group, an arylaminocarbonyl group wherein the aryl radical may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups and (C1-C4)alkyl groups, a N alkylarylaminocarbonyl wherein the alkyl radical has from 1 to 3 carbon atoms and the aryl radical may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups and (C1-C4)alkyl groups, an aminocarbonyl radical, or a mono- or di-alkylaminocarbonyl radical wherein the or each alkyl group has from 1 to 10 carbon atoms, R2 represents a hydrogen atom, a straight chain or branched chain (C1-C12)alkyl group, a benzyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from one or two chlorine atoms, trifluoromethyl groups, nitro groups and (C1-C4)alkyl groups, an alkoxycarbonyl radical having from 1 to 6 carbon atoms, a phenylthio group, a morpholino group, a piperidino group, or an arylamino group the aryl group of which may be unsubstituted or substituted by one or more (C1-C4)alkyl groups or R1 and R2 together represent -CH2CH2CH2CH2-, R3 represents a hydrogen atom or a (C1-C4)alkyl group, R4 represents a hydrogen atom or a straight chain or branched chain (C1-C12)alkyl group, R5 represents a hydrogen atom or a (C1-C4)alkyl group 130 represents a hydrogen atom or a (C1-C4)alkyl group and A represents one of the following groups:

wherein n is 2 or 3 and R7, R8, R9 and Y and Y' have the following meanings:: R7 represents a straight chain or branched chain (C1-C12)alkyl group, an arylmethyl group wherein the aryl moiety may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms and trifluoromethyl groups, a 2-furylmethyl group, a hydroxyethyl group, a jB- or y-hydroxypropyl group, a radical of the formula --CH,COOH, --CH(CH,)COOH, --CH,CH,COOH,

a phenyl radical which may be unsubstituted or substituted by one or more of the same or different substituents selected from hydroxy groups, nitro groups, (C1-C4)alkyl groups and-COOH groups, a a- or ss-naphthyl group or a cyclohexyl group, represents a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from one or two halogen atoms, trifluoromethyl groups, nitro groups, one or two (C1-C4)alkyl groups, dimethylamino groups, -COOCH3 groups, -COOC2H5 groups, a 4'-chlorophenoxy group, a 2'chlorophenoxy group, a 2',4'-dichlorophenoxy group, a 4'-phenoxy group, methoxy groups and ethoxy groups or represents a benzamido radical, a straight chain or branched chain alkyl group of the general formula

or -CH2CH2CH2R14 wherein R10 to R'4 have the following meanings:: R10 represents a hydrogen atom, a 2-furyl group, a ,-piperidino group, a phenyl group which may be substituted by one or more of the same or different substituents selected from a chlorine atom, (C1-C3)alkyl groups and a 3,4-dioxomethylene group, a dialkylamino group wherein each alkyl group has from 1 to 5 carbon atoms, a piperidyl group, a morpholino group, a bicycle-[2,2,1 ]-heptyl group or a cyclohexyl group, 1311 represents a hydrogen atom or a methyl group, R12 represents a hydrogen atom or a (C1-C3)alkyl group, R13 represents a phenyl group, a hydroxy group, a dialkylamino group having from 1 to 5 carbon atoms in each alkyl chain, a methoxy group or a hydroxyethylamino group, R14 represents a dialkyamino group having from 1 to 5 carbon atoms in each alkyl chain, a (C,C4)alkoxy group, a hydroxy group, a morpholino group, a N-methylpiperazino group, a hydroxyethylamino group, or a methylamino group, R9 represents a hydrogen atom or a hydroxyethyl group, or, when R8 represents a phenyl group, represents a straight chain or branched chain (C1-C6)alkyl group, or R8 and R9 together represent one of the following groups:: -N=CH-N=CH-, 7CH2CH20CH2CH2-, -CH2CH2CH2CH2-,

Y represents a C,V,8)alkyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from (C1-C3)alkyl groups, chlorine atoms, trifluoromethyl groups and nitro groups or which may be benzoannellated or a (C5-C8)cycloalkyl group, and Y' represents a hydrogen atom or, when Y represents a (C1-C4)alkyl group, a (C1-C4)alkyl group, or a salt thereof.

The ring nitrogen atom in the 1-position has basic properties and therefore a salt of a compound of the invention may be formed with an inorganic or organic acid at this position. A salt of a compound of the invention may, of course, be formed at any position where a salt-forming group is present; similarly an acid or a base may be formed at any suitable position in the compound.

Examples of salts with inorganic acids are phosphates, phosphites, chiorides, bromides, iodizes, sulphates, and examples of salts with organic acids e.g. mono- and poly-carboxylic acids are acetates, laurates, citrates, tartrates, oxalates, benzoates, sulphonates, or phosphonates.

The present invention further provides a process for the preparation of a compound of the general formula (I) which comprises reacting a compound of the general formula (II)

in which R' to 138 are defined as above with an equimolar amount of a mercaptan of the general formula (Ill) or with an equimolar to twofold equimolar amount of an amine of the general formula (IV)

wherein R7, R8 and R9 are defined as above, preferably in the presence or absence of an inert solvent, preferably at a temperature in the range of from 50 to 1 500C or in the range of from 130 to 2000 C, to give the hydrochloride compound and, if desired, converting the hydrochloride into a free base.

This reaction is preferably carried out in an inert non-polar solvent to which the halogen compound is added first, after which the nucleophilic compound is added at an elevated temperature.

The reaction may be accelerated by the addition of catalytic amounts of NH4CI. Suitable non-polar solvents are, for example, aliphatic hydrocarbons having a boiling point of up two 2000 C, toluene, xylene, dioxan and halohydrocarbons, e.g. chloroform, carbon tetrachloride, chlorobenzene or dichlorobenzene.

Toluene and xylene are preferred. It is also possible, if desired, to use polar solvents such as acetonitrile, dimethyl formamide or hexamethyl-phosphorus triamide, preferably the latter two, under the same conditions.

The reaction may be carried out at a temperature in the range of from 50 to 2000 C. A temperature in the range of from 50 to 1 500C is preferred for the reaction with the mercaptan, whereas the reaction with the amine is preferably carried out at a temperature in the range of from 130 to 2000C.

As mentioned above, the reaction may also be carried out in the absence of a solvent in the .respective temperature range.

The reaction of a 4-chloro-5,6,7,8-tetrahydroquinoline compound with the mercaptan is carried out with equimolar amounts of the latter, calculated on the chloro-compound, whereas the amines are used in equimolar to twofold equimolar amounts. If strongly basic amines are used, twofoid equimolar amounts are required.

The product is obtained in the form of the hydrochloride which may be converted into the free quinoline by reaction with a base, for example an organic tertiary base such as triethylamine or pyridine, and preferably with an inorganic base such as Na2CO3, K2CO3, NaOH, or KOH. For neutralisation the inorganic bases are preferably used in the form of solutions in polar solvents, for example alcohols.

In the reaction of cliloro-compound with amine the compounds of the invention are also obtained as the hydrochloride or in admixture with an aminehydrochloride. By treatment with suitable bases, for example NaOH or KOH, which are preferably used in alcoholic solution but which may also be used in aqueous solution, the amine may be recovered from the hydrochloride.

A further process is also provided by the present invention, which comprises reacting a compound of the general formula (I) wherein A represents the group 5137 wherein R7 represents a p-hydroxyethyl group, a p-hydroxypropyl group or a y-hydroxypropyl group or the group

wherein R9 represents a hydrogen atom and R8 represents a -hydrnxyethyl group, a /3-hydroxypropyl group or a 7hydrnxyprnpyl group with an equimolar amount of an isocyanate of the general formula (V) Y-N=C=O (V) wherein Y represents a (C1-C18)alkyl group or a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from (C1-C4)alkyl groups, chlorine atoms, trifluoromethyl groups or nitro groups or which may be benzoannellated, or a (C5-C6)cycloalkyl group, preferably in an inert solvent and in the presence of catalytic amounts of a base, or reacting said compounds with an equivalent amount of a dialkylcarbamic acid chloride of the general formula (VI)

wherein both Y and Y' represent a (C1-C4)alkyl group, preferably in an inert solvent and preferably in the presence of an equimolar amount of an auxiliary base, both reactions being preferably carried out at a temperature in the range of from 20 to 1 500 C.

To carry out the reaction with isocyanates the reaction components may be cornbined with an inert solvent, whereupon catalytic amounts of a base are added and the mixture heated to a temperature in the range of from 20 to 150 C, preferably from 40 to 140 C, for from 1 to 4 hours Suitable inert solvents are, for example, dioxan, toluene, xylene, acetonitrile, CH2CI2 or CHCl3.

Suitable basic catalysts are, for example, triethylamine or 1 ,4-diazabicyclo-[2,2,2]-octane, which may be used in an amount of 5 x 10-4 to 5 x 10-6 moles per mole of hydroxy compound to be reacted.

In some cases an excess of isocyanate of up to about 10 mole % may prove advantageous.

In the case of a reaction with a dialkylcarbamic acid chloride, the same conditions may be used with the exception that no catalyst is required. In this case, where no catalyst is used equimolar amounts of an auxiliary base must be added.

Suitable auxiliary bases are, for example, organic tertiary bases such as triethylamine or pyridine, or inorganic bases such as Na2CO3 or K2CO3. In this case, too, an acid chloride excess of up to about 10 mole % may prove advantageous.

Suitable isocyanates are, for example, methyl isocyanate, ethyl isocyanate, propyl isocyanate, butyl isocyanate, octadecyl isocyanate, phenyl isocyanate, cyclohexyl isocyanate, chlorophenyl isocyanate and naphthyl isocyanate.

Dialkylcarbamic acid chlorides which may be used are, for example, dimethylcarbamic acid chloride, diethylcarbamic acid chloride, dipropylcarbamic acid chloride and diphenylcarbarnic acid chloride.

The compounds of the invention may be purified, in part, by recrystallisation and, in part, by distillation, especially for the compounds of the invention in which A represents a

group wherein R9 represents an alkyl group. Compounds of this type are colourless or yellow, viscous oils.

The 4-chloro-5,6,7,8-tetrahydroquinolines of the general formula (II) used as starting compounds for the preparation of 5,6,7,8-tetrahydroquinolines of the general formula (I) may be produced by the process of E. Ochiai, M. Takahashi and R. Tanabe, Chem. Pharm. Bull. Soc. Jap. 15 (9), 1385 (1967), wherein 2-methyl-4-hydroxy-5,6,7,8-tetrahydroquinolines are reacted with POCI3.There are mentioned by way of example 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline, 4-chloro-5,6,7 ,8-tetrahydro quinoline, 4-chloro-2-methyl-6-isopropyl-5,6,7,8-tetrahydroquinoline, 4-chloro-2-n-propyl-8-isopropyl 5,6,7,8-tetrahydroquinoline, 4-chloro-2,6-dimethyl-5,6,7,8-tetrahydroquinoline, 9-chloro 1 ,2,3,4,5,6,7,B-octahydroacridine, 3,4-dichloro-2-methyl-5,6,7,8-tetrahydroquinoline, 4-chloro-2,8 dimethyl-5,6,7,8-tetrahydroquinoline and 4-chloro-3,6-dimethyl-5 6,7,8-tetrahydroquinolinyl-2- carboxylic acid methyl ester.

Suitable mercaptans for the reaction of the chloro-compounds are, for example, thiophenol, 2-furyl methanethiol, 2-thioglycerol, 4-chlorobenzylmercaptan, thiosuccinic acid, thioacetic acid, thiopropionic acid benzylmercaptan, pentachlorothiophenol, p-hydroxythiophenol, p-chlorothiophenol, p bromothiophenol, p-methylthiophenol, p-nitrothiophenol, 2-mercaptonaphthalene, thioglycol, thioacetic acid ester, thiobenzoic acid, 2-mercaptobenzoic acid, 4-bromo-3-methylthiophenol, 4-bromo-2 methylthiophenol, mercaptoacetic acid, 2,4,5-trichlorothiophenol and 2- or 3-mercaptopropionic acid.

Amines suitable for the reaction with the chloro-compounds are, for example, 3-dimethylamino propylamine, 3,4- and 3,5-dichloroaniline, N-methylaniline, 3-bromoaniline, 3-trifluoromethylaniline, 2,6-diisopropylaniline, 4-chloro-benzylamine, benzhydrazide, 1,2,4-triazole, P-hydroxyethylamine, p- hydroxypropylamine, y-hydroxypropylamine, N-ethyl-3-toluidine, N-propylaniline, N-butylaniline, N benzylaniline, y-methoxypropylamine, y-isopropoxypropylamine, 1 -methyl-1 -cyclohexylamine, bicyclo 2,2,1 )-hept-2-yl-methylamine, y-morpholinopropylamine! ,B-phenylethylamine, a-phenylethylamine, 2 furylmethylamine, exo-norborn-2-ylamine, 2,6-dimethylaniline, 2- or 4-isopropylaniline, 2,3- or 4 chloroaniline, 4-fluoroaniline, 4-n-butylaniline, naphthylamine, and cyclooctylamine.

The compounds of the invention are suitable for use as biocides. They have a relatively broad effect against, for example, fungi, bacteria and algae. They are especially effective against phytopathogenic fungi, for example types of mildew, Botrytis cinerea, rust fungi, Cercospora betae, Cladosporium fuivum, Fusicladium dentriticum and Rhizoctonia solani. They are also excellently suitable against oomycetes of organisms of the class of phycomycetes, for example Phytophthora, Peronospora, Pseudoperonospora, Plasmopara and Phythium.

The compounds are also effective against phytopathogenic bacteria such as Xanthomonas phaseoli, Xanthomonas oryzae, Xanthomonas citri, Xanthomonas malvacearum, Erwinia caratovora and Coryne-bacterium michiganense.

The compounds may also be successfully used against non-phytopathogenic fungi and bacteria growing on industrial substrata and decomposing or destroying same, for exampleAureobasidium pullulans, Ulocladium consortiale, Aspergillus niger, Penicillium funiculosum, Poria monticola and Coniophora puteana. They also may be used to control the growth of bacteria such as Escherichia coli, Bacillus subtllis and Aerobacter aerogenes. In addition, the compounds are effective against various types of algea, for example Chlorella vulgaris, Anabaena flosaquae, Spirogyro species and Enteromorpha species.

Accordingly the present invention further provides a biocidal preparation which comprises a compound of the invention in admixture or conjunction with a suitable carrier.

The compounds may be formulated in the usual manner as dusts, wettable powders, dispersions or emulsifiable concentrates. The content of active substances in these formulations is preferably in the range of from 10 to 90% by weight. In addition, the formulation may contain the usual adhesives, wetting agents, dispersing agents, fillers and carriers.

The present invention also provides a method of combating or controlling a fungal and/or bacterial and/or algal growth which comprises applying a compound of the invention or a biocidal preparation of the invention to the fungal and/or bacterial and/or algal growth, or to the locus thereof or to a substrate infested with or liable to infestation by a fungal and/or bacterial and/or algal growth.

The following Examples illustrate the invention.

EXAMPLE 1 4-Phenylthio-2-methyl-5,6, 7,8-tetrahydroquinoline 0.2 mole (22 g) of thiophenol was added to 0.2 mole (36.3 g) of 4-chloro-2-methyl-5,6,7,8- tetrahydroquinoline and the mixture was heated to 1 200C. The mixture was allowed to react whilst stirring, cooled, and taken up in 100 ml of toluene; 0.2 mole (20 g) of triethylamine was then added dropwise. Stirring was continued for 1 hour, the triethylamine hydrochloride was suction-filtered off and the mother liquor concentrated by evaporation under reduced pressure. The residue was triturated with ice whereby it crystallised out. 27 g of a product were recrystallised from n-hexane; melting point 1 160C.

EXAMPLE 2 4-(2 '-furylmeth ylthiol-2-methyl-5, 6, 7,8-tetrahydroquinoline 0.2 mole (36.3 g) of 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline and 0.2 mole (23 g) of 2furylmethylthiol were combined and heated to 140 to 1 500C. The mixture was allowed to react, cooled and taken up in 100 ml of toluene and 0.2 mole (20 g) of triethylamine. After stirring for 1 hour the salt was filtered off and the mother liquor was concentrated. After recrystallisation from heptane 21.4 g of a product, having melting point of 91 0C, were obtained.

EXAMPLE 3 4-(2 ',3 '-Dihydroxyl- 1 '-prop yithio)-2-methyi-5, 6, 7,8-tetrahydroquinollne hydrochloride 36.3 g (0.2 mole) of 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline were added dropwise at 1 400C to a solution of 21.9 g of 2-thioglycerol in 100 ml of xylene. After some time a white precipitate formed which was suction-filtered off. 38.0 of a compound having a melting point of 2040C were obtained. C13H20CINO2S; MW = 289.5 C H N calc. 53.9 6.9 4.8 found 53.6 6.9 4.6 The free base was obtained by dissolving 27.5 g of the hydrochloride in about 100 ml of methanol and neutralising the solution with an equimolar amount of sodium hydroxide. 22 g of a compound having a melting point of 1 590C were obtained.

C,3H19NO2S; MW= 253 C H N calc. 61.7 7.5 5.5 found 61.6 7.7 5.5 EXAMPLE 4 4-/4 '-Chlorobenzylthio)-2-methyl-5, 6, 7,8-tetrahydroquinollne 36.3 g of 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline were added dropwise at 1 400 C to a solution of 34 g (0.2 mole) of 4-chlorobenzylmercaptan in 100 ml of xylene; the hydrochloride formed after some time. It was suction-filtered off and neutralised in 20 ml of methanol with an equimolar amount of sodium hydroxide. 16.5 g of a compound having a melting point of 131 OC were obtained.

C"H,8CINS; MW = 303,5 C H N calc. 67.2 5.9 4.6 found 66.8 6.0 4.5 The following compounds were prepared in an analogous manner.

yield melting poind Example Compound (%) ( C) 5 4-(2-Methyl-5,6,7,8-tetrahydroquinollnyl)-thioosuccinic acid 54 240 6 4-(2-Methyl-5,6,7,8-tetrahydroquinollnyl)-thioacetic acid-hydrochloride 87 256 7 4-Benzylthio-2-methyl-5,6,7,8-tetrahydroquinoline 32 109 8 4-Pentachlorophenylthio-2-methyl-5,6,7,8-tetrahydroquinoline 53 176 9 4-(4'-Hydroxyphenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 47 128 10 4-(4'-Bromophenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 49 180-5 11 4-(4'-Methylphenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 28 85-7 12 4-(3',4',5',6'-Tetrahydropyrimidino-2'-)thio-2-methyl-5,6,7,8-tetrahydroquinoline. hydrochloride 22 171-4 13 4-(4'-Nitrophenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline, hydrochloride 34 232 14 4-(4'-Nitrophenythio)-2-methyl-5,6,7,8-tetrahydroquinoline 21 130-2 15 4-(4'-Chlorophenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 40 121 16 4-(2'-Naphthylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 86 95-6 17 4-(2-Methyl-5,6,7,8-tetrahydroquinoline)-thio-3'-propionic acid.hydrochloride 62 228 18 4-(2-Methyl-5,6,7,8-tetrahydroquinoline)-thio-2'-propionic acid.hydrochloride 82 110 19 4-(2'-Hydroxyethylthio)-2-methyl-5,6,7,8-tetrahydroquinoline hydrochloride 61 188 20 4-(2'-Hydroxyethylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 81 108-4 21 4-(2-Methyl-5,6,7,8-tetrahydroquinoline)-thioacetio acid methyl ester hydrochloride 64 200 22 4-(2-Methyl-5,6,7,8-tetrahydroquinoline)-thio-2'-benzoic acid hydrochloride 92 228

Yield melting point Example Compound (%) ( C) 23 4-Benzoylthio-2-methyl-5,6,7,8-tetrahydroquinoline hydrochloride 70 from 210 dec. 24 4-(4'-Bromo-3'-methylphenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline. hydrochloride 92 from 246 dec. 25 4-Acetylthio-2-methyl-5,6,7,8-tetrahydroquinoline 61 115 26 4-(2'-Thiazolinylthio)-2-methyl-5,6,7,8-tetrahydroquinoline.hydrochloride 22 297 dec. 27 4-(2',4',5'-Trichlorophenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 76 114 28 4-Propionylthio-2-methyl-5,6,7,8-tetrahydroquinoline 67 114 29 4-(2-Methyl-5,6,7,8-tetrahydroquinoline)-thio-2-benzoic acid 33 204 30 4-Benzoylthio-2-methyl-5,6,7,8-tetrahydroquinoline 68 75 31 4-(3'-Methyl-4'-bromophenylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 94 77

EXAMPLE 32 4-(3 '-Dimethyiami,iopropyi- 1 '-aminol-2-methyl-5, 6, 7,8-tetrahydroquinoline 61.2 g (0.6 mole) of 3-dimethylaminoproplamine and 72.6 g of 4-chloro-2-methyl-5,6,7,8- tetrahydroquinoline and catalytic amounts of NH4CI were heated for 15 hours to 1 600C. The mixture was cooled, taken up in methanol and neutralised with an equimolar amount of sodium hydroxide solution. The reaction mixture obtained was evaporated to dryness in vacuo and the free base was extracted with chloroform. The chloroform solution was dried with Na2SO4, filtered and evaporated in a rotary evaporator in vacuo. After vacuum distillation at 1 600C under a pressure of 0.2 mbar the remaining oil yielded 86.6 g of product.

C1SH2sN3; MW = 247 C H N calc. 72.9 10.1 17.0 found 72.4 10.3 16.6 EXAMPLE 33 4-(3 ',4 '-Dichloroanilinol-2-methyl-5, 6, 7,8-tetrahydroquinoline 54.3 g (0.3 mole) of 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline and 72.9 g (0.45 mole) of 3,4-dichloroaniline and catalytic amounts of NH4CI were heated for 12 hours to 160 to 1 700C. After this time the contents of the flask had solidified, the flask was cooled and the contents taken up in 100 ml of methanol. Next, they were neutralised with an equimolar amount of sodium hydroxide solution and the reaction mixture was digested with water. The product was filtered and dried in vacuo. About 61.6 g of product having a melting point of 1 700C were obtained.

The compound is crystailised from CCl4.

CtBH,6CI2N2; MW = 307 C H N calc. 62.5 5.2 9.1 found 62.5 5.2 8.9 EXAMPLE 34 4-(N-Methylanilinol-2-methyl-5,6, 7,8-tetrahydroquinoilne 36.3 g (0.2 mole) of 4-chloro-tetrahydroquinoline, 21.5 g (0.2 mole) of N-methylaniline and catalytic amounts of NH4Cl were heated to 1 800C for 4 hours, the mixture was cooled and 100 ml of methanol were added. The mixture was then neutralised with an equimolar amount of sodium hydroxide solution, the solvent removed in a rotary evaporator, the residue taken up in chloroform, and the solution dried with Na2SO4 and filtered. The chloroform was evaporated off and the residue was distilled at 136 and 1 380C under a pressure of 0.13 mbar. The yield amounted to 34.5 g.

C1,H20N2; MW = 252 C H N calc. 81.0 7.9 11.1 found 80.8 8.0 11.3 EXAMPLE 35 4-(3'-Chloroanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 22.3 g (0.1 mole) of 4-chloro-2-methyl-6-isopropyl-5,6,7,8-tetrahydroquinoline, 12.8 g (0.1 'mole) of 3-chloroaniline and catalytic amounts of NH4CI were heated for 3 hours to 160 to 1 760C. The viscous mass was cooled, taken up in 100 ml of methanol and an equimolar amount of sodium hydroxide solution added. The mixture was evaporated under reduced pressure, taken up in chloroform and the solution dried with Na2SO4. It was filtered, the chloroform evaporated and the reaction product recrystallised from CCl4. 10 g of a product having a melting point of 1 640C were obtained.

CrgH23CIN2; MW = 314,5 C H N calc. 72.5 7.3 8.9 found 73.1 7.2 8.9 EXAMPLE 36 4-(3',4'-Dichloroanilino)-2-n-propyl-8-isopropyl-5,6,7,8-tetrahydroquinoline 25.15 g (0.1 mole) of 4-chloro-2-n-propyl-8-isopropyl-5,6,7,8-tetrahydroquinoline, 16.2 g (0.1 mole) of 3,4-dichloroaniline and catalytic amounts of NH4CI were heated for 7 hours to 160 to 1 700 C.

The viscous mass was dissolved in 100 ml of methanol and an equimolar amount of 0.1 M sodium hydroxide solution was added. The mixture was concentrated to dryness and taken up in chloroform.

The solution was dried with Na2SO4 and filtered. The filterate was evaporated in a rotary evaporator and the residue was recrystallised from CCl4. 27 g of product having a melting point of 11 00C were obtained.

C2rH26CI2N2; MW = 377 C H N calc. 66.8 6.9 7.4 found 66.9 7.0 7.5 EXAMPLE 37 4-(3'-Trifluromethylanillino)-2,6-dimethyl-5,6,7,8-tetrahydroquinoline 15.6 g (0.08 mole) of 4-chloro-2,6-dimethyl-5,6,7,8-tetrahydroquinoline, 12.9 g (0.08 mole) of trifluoromethylaniline and catalytic amounts of NH4CI were heated to 1 750C, whereupon the mass became viscous and finally solidified. The reaction mixture was worked up as described in Example 36 and the reaction product was recrystallised from CCl4. 11.5 g of a compound having a melting point of 131 0C were obtained.

EXAMPLE 38 9-13:4 '-DichloroanilinoJ- 1,2,3,4,5,6, 7,8-octahydroacridine 17.4 g (0.1 mole) of 9-chloro-1 ,2,3,4,5,6,7,8-octahydroacridine, 13 g of 3,4-dichloroaniline and catalytic amounts of NH4CI were heated for 7 hours to 1800 C. The solid formed on cooling was worked up as described in Example 36 and the reaction product was recrystallised from CCl4. 10.2 g of a compound having a melting point of 1 020C were obtained.

C1gH20CI2N2; MW = 347 EXAMPLE 39 4-(3',4-Dichloroanilino)-3-chloro-2-methyl-5,6,7,8-tetrahydroquinoline 21.6 g (0.1 mole) of 3,4-dichloro-2-methyl-5,6,7,8-tetrahydroquinoline, 16.2 g (0.1 mole) of 3,4dichloroaniline and catalytic amounts of NH4CI were heated for 4 hours to 180 to 1 850C, whereupon the mass solidified. The reaction product was worked up as described in Example 36 and the reaction was recrystallised from CCI4. 33.2 g of a compound having a melting point of 1 230C were obtained.

EXAMPLE 40 4-(2 ',6'-DiisopropylanilinoJ-2,8-dimethyl-5,6, 7,8-tetrabydroquinoline 19.6 g (0.1 mole) of 4-chloro-2,8-dimethyl-5,6,7,8-tetrahydroquinoline, 11.7 g (0.1 mole) of 2,6diisopropylaniline and catalytic amounts of NH4CI were heated for 8 hours to 1 900C. The cooled and solidified mass was worked up as described in Example 36 and distilled in a high vacuum. 1 6 go of compound were obtained at 1 900C under a pressure of 0.07 mbar.

EXAMPLE 41 4-(4 '-Chlorobenzylaminol-3, li-dimethyl-ti, 6, 7,8-tetrahydroquinolinyl-2-carboxylic acid methyl ester 25.35 g (0.1 mole) of 4-chloro-3,6-dimethyl-5,6,7,8-tetrahydroquinolinyl-2-carboxylic acid methyl ester, 18.4 g (0.13 mole) of 4-chlorobenzylamine and catalytic amounts of NH4CI were heated for about 17 hours to 165 to 1 700 C. The reaction mixture was worked up as described in Example 36 and the residue was distilled in a high vacuum. 8.5 g of compound were obtained at 190 to 2000C under a pressure of 0.24 mbar.

C20H23CIN202; MW =358.5 C H N calc. 66.9 6.4 7.8 found 67.8 6.6 8.2 EXAMPLE 42 4-N-(N'-Benzoylhydroazino)-2-methyl-5,6,7,8-tetrahydroquinoline hydrochloride 36.3 g (0.2 mole) of 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline, 27.3 g (0.2 mole) of benzhydrazide and catalytic amounts of NH4CI were stirred at 1 350C until the reaction starts. The mixture was cooled and digested with acetone. 53.7 g of a compound having a melting point of 31 20C were obtained.

C17H20ClN3O; MV = 317.5 C H N calc. 64.3 6.0 13.2 found 64.0 5.9 13.3 EXAMPLE 43 4- Triazolyl-2-methyl-5, 6, 7,8-tetrahydroquinoline 36.3 g (0.2 mole) of 4-chloro-2-methyl-5,6,7,8-tetrahydroquinoline, 14 g (0.2 mole) of 1,2,4 triazole and catalytic amounts of NH4CI were heated for 30 minutes to 1600 C. The mixture was allowed to cool, taken up in 100 ml of ethanol and an equimolar amount of sodium hydroxide solution was added. The solvent was evaporated in a rotary evaporator and the residue taken up in chloroform.After filtration the chloroform was distilled off. 26.2 g of a solidifying oil having a melting point of 69 to 750C were obtained. C,2H,4N4; MW = 214 The compounds specified in the following table were prepared in an analogous manner to Examples 32 to 41.

Yield bioling point or Example Compound (%) melting point ( C) 44 4-(3'-Diethylaminopropyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 64 170/0.65 mbar 45 4-(2'-Diethylaminoethyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 78 160-165/0.2 mbar 46 4-(2'-Dimethylaminoethyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline. hydrochloride 48 279 47 4-(2'-Hydroxyethyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 93 154-6 48 4-(4'-Chloroanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 32 153-4 49 4-(Cyclooctylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 49 84 50 4-(Cyclohexylmethylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 69 85 51 4-(4'-Tert-butylcyclohexyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 11 185/0.65 mbar 52 4-(4'-Chlorobenzylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 68 179 53 4-(4'-Cyanobenzylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 88 130 54 4-(N-Ethyl-3'-methylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 61 152-7/0.53 mbar 55 4-(N-Propylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 92 oil 56 4-(N-Butyllanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 59 157-180/0.53 mbar 57 4-(3'-Methoxypropyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 53 161/0.13 mbar 58 4-(3'-isopropoxypropyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 76 160/0.13 mbar 59 4-(1'-Methyl-1'-cyclohexylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 86 65-70 60 4-[Bicyclo-(2,2,1)-hept-2'-yl-methylamino]-2-methyl-5,6,7,8-tetrahydro quinoline 78 90

Yield bioling point or Example Compound (%) melting point ( C) 61 4-(3'Hydroxypropyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 30 149 62 4-(3'Morphollnopropyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 73 187/0.065 mbar 63 4-(2'-Methoxyethyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 71 130-136/0.13 mbar 64 4-(2'-Phenylethyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline 70 112-13 65 4-(1'-Phenylethyl amino)-2-methyl-5,6,7,8-tetrahydroquinoline 72 94-8 66 4-(Furfur-2'-ylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 72 115 67 4-(N'-Hydroxyethylamino-3'-propyl-1'-amino)-2-methyl-5,6,7,8-tetrahydro quinoline 81 200-5/0.4 mbar 68 4-(N'-Hydroxyethylamino-2'-ethyl-1'-amino-2-methyl-5,6,7,8-tetrahydro quinoline 76 190-200/0.8 mbar 69 4-(N-Ethylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 17 144-5 70 4-(Piperid-4'-ylmethylamino)-2-methyl-5,6,7,8-tetrahydroquinoline. hydrochloride 15 337 71 4-(3'-Methylaminopropyl-1'-amino)-2-methyl-5,6,7,8-tetrahydroquinoline hydrochloride 83 oil 72 4-(3',5'-Dichloroanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 54 195 73 4-(3'-Chloroanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 72 193-5 74 4-(3'-Trifluoromethylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 84 136-8 75 4-(4'-Methoxyanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 41 135 76 4-(N-Benzylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 31 164-170/0.8 mbar

Yield boiling point or Example Compound (%) melting point ( C) 77 4-(2',6'-Dimethylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 80 157-161 78 4-(2'-Isopropylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 81 157-159 79 4-(4'-Ethoxycarbonylphenylamino)-2-methyl-5,6,7,8-tetrahydroquinoline hydrochloride 81 70 80 4-(4'Isopropylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 91 140-2 81 4-[4'-(2",4"-Dichlorophenoxy)-anilino]-2-methyl-5,6,7,8-tetrahydro quinoline 97 128-131 82 4-(2'-Methyl-5'-chloro-anilino)-2-methyl-5,6,7,8-tetrahydroquinoline 98 220-230 83 4-(2'-Methyl-4'-chloro-anilino)-2-methyl-5,6,7,8-tetrahydroquinoline 68 241-3 84 4-(Exo-norborn-2'-ylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 50 82 85 4-(3'-Methylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 92 17-26 86 4-(4'-Methylanilino)-2-methyl-5,6,7,8-tetrahydroquinoline 94 156-8 87 4-(3',4'-Dimethoxyphenylethyl-1"-amino)-2-methyl-5,6,7,8-tetrahydro quinoline=hydrochloride 80 173 88 4-(4'-isopropylanilino)-2-n-propyl-8-isopropyl-5,6,7,8-tetrahydroquinoline 74 193-5/0.04mbar 89 4-(2'-Isopropylanilino)-2-n-propyl-8-isopropyl-5,6,7,8-tetrahydroquinoline 63 195-210/0.13 mbar 90 4-(3'-Trifluoromethylanilino)--2-n-propyl-8-isopropyl-5,6,7,8-tetrahydro quinoline 94 97 91 4-(3'-Chloroanilino)-2-n-propyl-8-isopropyl-5,6,7,8-tetrahydroquinoline 63 185-192/0.13 mbar 92 4-(N-Methylanilino)-2-n-propyl-8-isopropyl-5,6,7,8-tetrahydroquinoline 70 150-5/0.065 mbar

Yield boiling point or Example Compound (%) melting point ( C) 93 4-(4'-Isopropylanilino)-2-methyl-6-isopropyl-5,6,7,8-tetrahydroquinoline 68 158 94 4-(N-Propylanilino)-2-methyl-6-isopropyl-5,6,7,8-tetrahydroquinoline 66 140-155/0.065 mbar 95 4-(3',4'-Dichloroanilino)-2-methyl-6-isopropyl-5,6,7,8-tetrahydroquinoline 68 188 96 4-(2'-Methyl-4'-chloroanilino)-2-methyl-6-isopropyl-5,6,7,8-tetrahydro quinoline 68 208 97 4-(2',6'-Dimethylanilino)-2-methyl-8-isopropyl-5,6,7,8-tetrahydroquinoline 72 158 98 4-(1'-Methylcyolohexyl-1'-methylamino)-2-methyl-6-isopropyl-5,6,7,8 tetrahydroquinoline 64 170-182/0.065 mbar 99 4-(3',4'-Dichloroanilino)-2,6-dimethyl-5,6,7,8-tetrahydroquinoline 54 153 100 4-(2'-Ethylanilino)-2,6-dimethyl-5,6,7,8-tetrahydroquinoline 13 135-7 101 4-(N-Butylanilino)-2,6-dimethyl-5,6,7,8-tetrahydroquinoline 32 153-160/0.13 mbar 102 9-[Bloyclo-(2,2,1)-Hept-2'-ylexo-methylamino]-1,2,3,4,5,6,7,8-octa hydroacridine 27 170-200/0.065 mbar 103 4-(3',4'-Dichloroanilino)-2,3-dimethyl-5,6,7,8-tetrahydroquinoline 65 98 104 4-(3',5'-Dichloroanilino)-2,3-dimethyl-5,6,7,8-tetrahydroquinoline 70 99 105 4-(3'-Trifluoromethylanilino)-2-methyl-5,6,7,8-tetrahydro quinoline 50 56 106 4-(2',6'-Dimethylanilino)-2-methyl-3-chloro-5,6,7,8-tetrahydroquinoline 30 208/0.27 mbar 107 4-(3',4'-Dichloroanilino)-2,8-dimethyl-5,6,7,8-tetrahydroquinoline 67 195-210/0.2 mbar 108 4-(3'-Chloroanilino)-2,8-dimethyl-5,6,7,8-tetrahydroquinoline 63 152

yield boiling point or Example Compound (%) melting point ( C) 109 4-(4'-Isopropylanilino)-2,8-dimethyl-5,6,7,8-tetrahydroquinoline 18 134 110 4-[Bicyclo-(2,2,1)-hept-2-yl-exo-methylamino]-2,8-dimethyl-5,6,7,8-tetra hydroquinoline 32 161/0.065 mbar 111 4-(4'-n-Butylanilino)-2,8-dimethyl-5,6,7,8-tetrahydroquinoline 81 214/0.065 mbar 112 4-(2',6'-Dimethylanilino)-2,8-dimethyl-5,6,7,8-tetrahydroquinoline 40 146 113 4-(3'-Trifluoromethylanilino)-2,8-dimethyl-5,6,7,8-tetrahydroquinoline 86 118 114 4-(3'-Trifluoromethylanilino)-3,6-dimethyl-2-(5,6,7,8-tetrahydroquinolinyl carboxylic acid methyl ester 10 149 115 4-(4'-Isopropylanilino)-3,6-dimethyl-2-(5,6,7,8-tetrahydroquinolinyl carboxylic acid methyl ester 26 152 116 4-(4'-Chlorobenzylamino)-3,6-dimethyl-2-(5,6,7,8-tetrahydro)-quinolinyl carboxylic acid methyl ester 27 200-6/0.24 mbar 117 4-(N-Methylanilino)-3,6-dimethyl-2-(5,6,7,8-tetrahydro)-quinoline carboxylic acid methyl ester 15 253/0.2 mbar 118 4-(4'Isopropylanilino)-2-phenyl-5,6,7,8-tetrahydroquinoline 87 158 119 4-(4'-Chlorophenylthio)-2-phenyl-5,6,7,8-tetrahydroquinoline 98 84 120 4-(4'-Isopropylanilino)-2-methyl-3-morpholine-5,6,7,8-tetrahydroquinoline 64 oil 121 4-(4'-Isopropylanilino)-3-phenyl-5,6,7,8-tetrahydroquinoline 69 147 122 4-(4'-Bromophenylthio)-3-phenyl-5,6,7,8-tetrahydroquinoline 74 131 123 4-(2'-Furfurylmethylthio)-3-phenyl-5,6,7,8-tetrahydroquinoline 52 58

EXAMPLE 124 4-(Octadecylcarbamoyoxoethylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 20.7 g (0.1 mole) of 4-(hydroxyethylamino)-2-methyl-5,6,7,8-tetrahydroquinoline, 29.5 g of octadecyl isocyanate and catalytic amounts of 1 ,4-diazabicyclo-[2,2,2]-octane in 100 ml of toluene were refluxed for 3 hours. After cooling, the solution was concentrated. After some time a solid separated which was suction-filtered off and dried. Yield 39.3 g, melting point 940 C.

EXAMPLE 125 4-(Phenylcarbamoyoxyethylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 11.9 g (0.1 mole) of phenylisocyanate were added at 1000Cto a mixture of 21.9 g (0.1 mole) of 4-(hydroxyethylthio)-2-methyl-5,6,7,8-tetrahydroquinoline and catalytic amounts of 1,4-diazabicyclo- [2,2,2]-octane in 100 ml of toluene. Stirring at reflux temperature was continued for 2 hours the admixture cooled and the solution concentrated in vacuo to half of its original volume. Yield 32.5 g.

melting point 145 to 146DC.

The following compounds were prepared in an analogous manner.

yield boiling point or Example Compound (%) melting point ( C) 126 4-(Cyclohexylcarbamoyloxyethylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 76 150-1 127 4-(Ethylcarbamoyloxyethylthio)-2-methyl-5,6,7,8-tetrahydroquinoline 82 139-142 128 4-(Cyclohexylcarbamoyloxyethylamino)-|2-methyl|-5,6,7,8-tetrahydroquinoline 88 117-9 129 4-(Cyclohexylcarbamoyloxypropylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 80 107-8 130 4-(Phenylcarbamoyloxyethylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 94 143-4 131 4-(4'-Chlorophenylcarbamoyloxyethylamino)-[2-methyl-5,6,7,8-tetrahydro quinoline 96 178 132 4-(1'-Naphylcarbamoyloxypropylamino)-2-methyl-5,6,7,8-tetrahydroquinoline 73 160-2 133 4-(4'-Chlorophenylcarbamoyloxy-2'-propylamino)-2-#methyl-5,6,7,8-tetrahydro quinoline 80 148

The following Examples 134 to 142 are included to demonstrate the biological activity of the compounds of the invention. The letters A to M indicate the following comparison substances: A = manganese ethylene-1,2-bisdithiocarbamate (Maneb) B = N-(trichloromethylthio)-phthalimide C = Maneb-Zineb mixture (Mancozeb) D = Methyl-1-(butylcarbamoyl)-2-benzimidazole carbamate (Benomyl) E = Mergal S40 F = Mergal AT liquid G = Mergal CAB 40 H = MergalAF J = 2-(methoxycarbonylamino)-benzimidazole K = Mergal S 88 (zinc dithiocarbamate + substance = J) L = pentachlorophenol M = alkyl dimethylbenzyl ammonium chloride (Dimanin A) Mergal is a trade mark.Maneb is manganese ethylene-1,2-bisdithiocarbamate and Zineb is zinc ethylene -1 ,2-bisdithiocarbamate.

EXAMPLE 134 Tomato plants (Solanum lycopersicum), variety "Rheinlands Ruhm", were sprayed at the threeleaf stage to the drip off with the compounds indicated in Table 1 in concentrations of 500, 250, 125 and 60 mg of active substance per litre of spray liquor. Comparison substance A was used in the same concentrations.

After drying off the spray liquor, the plants were inoculated with a zoosporangium suspension of Phytophthora infestans and the plants, wet to the drip-off point, were kept for one day in a climatic chamber at a temperature of 1 50C and a relative humidity of 100%. They were then transferred to a cold greenhouse having a temperature of 1 50C and a relative humidity of 85 to 95%.

After an incubation time of 7 days, the plants were inspected as to their infestation with Phytophthora. The degree of infestation is expressed as a percentage of infested leaf area in comparison with untreated, infested plants.

TABLE 1

% infestation with Phytophthora with mg of active substance per litre of spray liquor Compound of Example 500 250 125 60 33 0 0-3 5 5-10 60 0 0 0 5 62 0 0-3 5 5-10 59 0 0 0-3 5 74 0 0 0 3-5 73 0 0 0-3 5 34 0 0 0-3 5 80 0 0 0 0 132 0 0 0-3 5 comparison 0 3 5 15 substance A untreated, 100 infested plants EXAMPLE 135 Vine cuttings of the type Müller-Turgau sensitive to Plasmopara were sprayed to the drip-off point at the four-ieaf stage with aqueous suspensions of compounds of the invention in concentrations of 500,250, 125 and 60 mg of active substance per litre of spray liquor.

After drying off the spray liquor, the plants were inoculated with a zoosporangium suspension of Plasmopara viticola and the plants, wet to the drip-off point, were placed in a climatic chamber at a temperature of 200C and a relative humidity of 10096. After 24 hours the plants were transferred to a greenhouse of 230C and a relative humidity of about 80 to 9096.

After an incubation time of 7 days, the plant were wetted, and placed overnight in a climatic chamber for development of the disease. The degree of infestation is expressed as a percentage of infested leaf area in comparison with untreated, infested control plants. The results are given below in Table 2.

TABLE 2

% infestation with Plasmopara viticola with mg of active substance per litre of spray liquor Compound of Example 500 250 125 60 33 0 0 0 5 80 0 0 3 5 78 0 0 3 5 comparison substance B 0 3 5 10 C 5 10 25 35 untreated, 200 infested plants EXAMPLE 136 Cucumber plants of the variety Delikatess were strongly infested at the 2-leaf stage with a conidia suspension of cucumber mildew (Erysiphe cichoracearum).After a drying time of the spore suspension of 30 minutes, the plants were placed in a greenhouse at 220C and 90% of relative humidity. 3 days after infestation the plants where sprayed to the drip-off point with the compounds and in the concentrations indicated in Table 3. The plants were examined 10 days after treatment. The degree of infestation is expressed as a percentage of infested leaf area in comparison with untreated, infested control plants (= 100%).

TABLE 3

% infestation with cucumber mildew with mg of active substance per litre of spray liquor Compound of z . Example 500 250 | 125 60 30 51 0 0 0-3 5 5-10 69 0 0 0 0-3 5 comparison substance D 3 5 10 15 25 untreated, 100 infested plants

EXAMPLE 137 A bacteria suspension of Bacillus sub tills was applied in drop form in 0.02 ml drops onto a culture media (standard I nutrient agar-agar for bacteria) in Petri dishes to which the compounds of the invention in the concentrations indicated in Table 4 had been added while the agar was still liquid.

The dishes were evaluated 4 days after inoculation with the bacteria and the inhibition of growth was ascertained as a comparison with a control dish (inoculated agar-agar without addition of active substance = 0% inhibition).

As comparison substances commercial products E, F, G, H free from mercury were used which were applied in the same active substance concentrations.

TABLE 4

inhibition in % of Bacillus subtilis with mg of active substance per litre of agar-agar Compound " Example 1000 500 100 50 I 10 61 100 100 100 50 59 100 100 80 50 81 100 100 100 100 50 133 100 100 100 100 50 131 100 100 100 100 80 50 100 100 80 50 51 100 100 100 100 50 49 100 100 100 50 - 52 100 100 80 50 55 100 100 100 100 50 comparison substance E 50 25 - - F 50 . 25 - - G 100 50 - - H 50 25 - - indicates that no experiment was carried out.

EXAMPLE 138 In an analogous manner to that described in Example 137 the inhibition of growth ofAerobacter aerogenes was examined.

TABLE 5

inhibition in % of Aerobacter aerogenes with mg of active substance per litre of agar-agar Compound of Example 1000 500 100 60 100 50 0 59 100 50 0 65 100 50 0 86 100 80 0 50 100 100 50 49 100 80 0 comparison substance J 50 50 0 H 50 50 0 K 50 50 0 EXAMPLE 139 A spore suspension of Ulocladium consortiale was applied in drop form in 0.02 ml drops onto a culture medium (biomalt agar-agar for fungi) in Petri dishes to which the compounds of the invention in the concentrations indicated in Table 6 had been added whilst the agar was still liquid. 6 days after inoculation, the diameter of the fungal colonies was measured and the inhibition of growth caused by the preparations expressed in % calculated on the control (inoculated agar-agar without active substance addition = 100%). For comparison commercial mercury-free products (E, F, G, H) were used in the same concentrations as the compounds of the invention.

TABLE 6

% inhibition of Ulocladium consortiale with mg of active substance per litre of agar-agar Compound of Example 1000 500 100 50 10 5 1 0.5 51 100 100 100 100 80 60 50 0 49 100 100 100 80 50 30 0 0 69 100 100 100 80 50 30 0 0 55 100 100 100 50 30 0 0 0 comparison substance E 100 100 100 80 30 0 0 0 F 100 20 0 0 0 0 0 0 G 100 100 60 0 0 0 0 0 H 100 100 80 0 0 0 0 0 EXAMPLE 140 In the manner described in Example 139 the inhibition of growth ofAureobasidium pullulans was examined.

TABLE J

% inhibition of Aureobasidium pullulans with mg of active substance per litre of agar-agar Compound of Example 1000 500 100 50 10 51 100 100 100 80 30 49 100 100 100 50 0 52 100 100 100 80 50 69 100 100 100 50 30 55 100 100 100 50 0 84 100 100 100 80 30 comparison substance L 100 100 50 - - - indicates that no experiment was carried out.

EXAMPLE 141 0.04 ml each of a spore suspension of Xanthomonas citri was applied in drop form on a culture medium (biomalt agar-agar for fungi) in Petri dishes to which the compounds in the concentrations indicated in Table 8 had been added whilst the agar-agar was still liquid. After 4 days the inoculated dishes were evaluated and the inhibition of growth was ascertained in comparison with a control dish (inoculated agar-agar without addition of active substance = 0% inhibition).

TABLE 8

% inhibition of Xanthomonas citri with mg of active substance per litre of agar-agar Compound of Example 250 125 60 30 15 48 100 100 100 50 40 33 100 100 100 80 50 EXAMPLE 142 The monocellular green alga Chiorella vulgaris was treated in a culture solution (according to Döhier) in the logarithmic phase of growth with the compounds indicated in Table 9 in concentrations of 10 and 2.5 ppm of active substance. Each time 30 ml of algae suspension was treated in an 100 ml Erlenmeyer flask.The flasks were kept on a shaking device with permanent movement (about 75 rpm) under permanent light (about 3,000 Lux). Table 9 shows the rate of inhibition in % in comparison with an untreated control. The suspensions were examined 1 0 days after treatment.

TABLE 9

algicidal effect against Chlorella vulgaris inhibition in % with ppm of active substance Compound of Example 10 2.5 48 100 95 60 100 100 59 100 97 80 100 100 78 97 95 130 100 90 131 100 90 50 100 100 52 100 97 54 100 85 55 100 100 comparison substance M 100 30

Claims

1. A compound of the general formula (I)

in which R1 represents a hydrogen atom, a straight chain or branched chain (C1-C12)alkyl radical, a benzyl or phenyl radical which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl radicals and (C1-C4)alkyl groups, a (C1-C0)alkoxycarbonyl radical, an arylaminocarbonyl radical wherein the aryl radical may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl radicals and (C1-C4)alkyl groups, a N-alkyl-arylaminocarbonyl radical wherein the alkyl radical has from 1 to 3 carbon atoms and the aryl radical may be unsubstituted or substitutedby one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups and (C14)alkyl groups, an aminocarbonyl radical, or a mono- or dialkylaminocarbonyl radical wherein the or each alkyl group has from 1 to 10 carbon atoms, R2 represents a hydrogen atom, a straight chain or branched chain (C1-C12)alkyl group, a halogen atom, a benzyl group or phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups, nitro groups and (C1C4)aikyl groups. an alkoxycarbonyl radical wherein the alkyl group has from 1 to 6 carbon atoms, a phenylthio group, a morpholino group, a piperidino group, or an arylamino group the aryl group of which may be unsubstituted or substituted by one or more (C1-C4)alkyl groups or R1 and R2 together represent -CH2CH2CH2CH2-, R3 represents a hydrogen atom or a (C1-C4)alkyl group, R4 represents a hydrogen atom or a straight chain or branched chain (C1-C12)alkyl group, R5 represents a hydrogen atom or a (C1-C4)alkyl group, R5 represents a hydrogen atom or a (C1-C6)alkyl group and A represents one of the following groups::

wherein n is 2 or 3 and R7, R8, R9 and Y and Y' have the following meanings: R7 represents a straight chain or branched chain (C1 (::12)alkyl group, an arylalkyl group wherein the aryl moiety may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms and trifluoromethyl groups, a furyialkyl group, a hydroxyalkyl group, a radical of the formula -CH2COOH, -CH(CH3)COOH, -CH2CH2COOH,

R6 represents a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups, nitro groups, (C1--C4)alkyl groups, dimethylamino groups, -COOalkyl groups, alkoxy groups, phenoxy groups and halogen-substituted phenoxy groups, a benzamido group, a cycloalkyl group, a straight chain or branched chain alkyl group of the general formula

14 or -CH2CH2CH2R@ wherein R10 to R14 have the following meanings:: R10 represents a hydrogen atom, a furyl group, a piperidino group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, (C1-C4)alkyl groups, cyano groups, and diomethylene groups, a dialkylamino group wherein each alkyl group has frorn 1 to 5 carbon atoms, a piperidyl group, a morpholino group, a bicyclo-[2,2,1]-heptyl group or an unsubstituted or substituted cyclohexyl group, R1' represents a hydrogen atom or a (C1-C4)alkyl group, R12 represents a hydrogen atom or a (C1-C4)alkyl group, R13 represents a hydroxy group, a dialkylamino group having from 1 to 5 carbon atoms in each alkyl chain, an alkoxy group, a hydroxyalkylamino group, or an unsubstituted or substituted phenyl group, R14 represents a dialkylamino group having from 1 to 5 carbon atoms in each alkyl chain, a (C1-C4)alkoxy group, a hydroxy group, a morpholino group, a N-alkylpiperazino group, an alkylamino group or a hydroxyalkylamino group, R9 represents a hydrogen atom, a straight chain or branched chain (C1-C5)alkyl group (when R6 represents a phenyl group), a hydroxyalkyl group or a benzyl group, or R8 and R9 together represent one of the following groups:: -N=CH-N=CH-, -CH2CH2OCH2CH2-, -CH2CH2CH2CH2-,

Y represents a C1-C16)alkyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from (C1-C3)alkyl groups, halogen atoms, trifluoromethyl groups and nitro groups or which may be benzoannellated, or a (C5-C6)cycloalkyl group, and Y' represents a hydrogen atom or may also represent a (C1-C4)alkyl group when Y represents a (C1C4)alkyl group.

2. A compound of the general formula

in which R represents a hydrogen atom, a straight chain linear or branched chain (C1-C12)alkyl group, a benzyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from one or two chlorine atoms, trifluoromethyl groups and (C1-C4)aikyl groups, a (C1-C6)alkoxycarbonyl group, an arylaminocarbonyl group wherein the aryl radical may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups and (C1-C4)alkyl groups, a N alkylarylaminocarbonyl wherein the alkyl radical has from 1 to 3 carbon atoms and the aryl radical may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms, trifluoromethyl groups and (C1-C4)alkyl groups, an aminocarbonyl radical or a mono- or di-alkylaminocarbonyl radical wherein the or each alkyl group has from 1 to 10 carbon atoms, R2 represents a hydrogen atom, a straight chain or branched chain (C1-C12)alkyl group, a benzyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from one or two chlorine atoms, trifluoromethyl groups, nitro groups and (C1-C4)alkyl groups, an alkoxycarbonyl radical having from 1 to 6 carbon atoms, a phenylthio group, a morpholino group, a piperidino group, or an arylamino group and the aryl group of which may be unsubstituted or substituted by one or more (C1-C4)alkyl groups or R and R2 together represent -CH2CH2CH2CH2-, R3 represents a hydrogen atom or a (C1-C4)alkyl group, R4 represents a hydrogen atom or a straight chain or branched chain (C1-C12)alkyl group, R5 represents a hydrogen atom or a (C1-C4)akyl group, R6 represents a hydrogen atom or a (C1-C6)alkyl group and A represents one of the following groups:

wherein n is 2 or 3 and R7, R8, R9 and Y and Y have the following meanings: : R7 represents a straight chain or branched chain (C1-C6)alkyl group, an arylmethyl group wherein the aryl moiety may be unsubstituted or substituted by one or more of the same or different substituents selected from halogen atoms and trifluoromethyl groups, a 2-furylmethyl group, a hydroxyethyl group, a ,B- or y-hydroxypropyl group, a radical of the formula -CH2COOH, -CH(CH3)COOH, -CH2CH2COOH,

a phenyl radical which may be unsubstituted or substituted by one or more of the same or different substituents selected from hydroxy groups, nitro groups, (C1-C4)alkyl groups and -COOH groups, a an or ss-naphthyl group or a cyclohexyl group, represents a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from one or two halogen atoms, trifluoromethyl groups, nitro groups, one or two (C1-C4)alkyl groups, dimethylamino groups, -COOCH3 groups, -COOC2H5 groups, a 4'-chlorophenoxy group, a 2'chlorophenoxy group, a 2',4'-dichlorophenoxy group, a 4'-phenoxy group, methoxy groups and ethoxy groups or represents a benzamido radical, a straight chain or branched chain alkyl group of the general formula

or -CH2CH2CH2R14 wherein R10 to R14 have the following meanings:: R10 represents a hydrogen atom, a 2-furyl group, a ss-piperidino group, a phenyl group which may be substituted by one or more of the same or different substituents selected from a chlorine atom, (C1-C3)alkyl groups and a 3,4-dioxomethylene group, a dialkylamino group wherein each alkyl group has from 1 to 5 carbon atoms, a piperidyl group, a morpholino group, a bicyclo-[2,2,1]-heptyl group or a cyclohexyl group, R11 represents a hydrogen atom or a methyl group, R12 represents a hydrogen atom or a (C1-C3)alkyl group, R13 represents a phenyl group, a hydroxy group, a dialkylamino group having from 1 to 5 carbon atoms in each alkyl chain, a methoxy group or a hydroxyethylamino group, R14 represents a dialkylamino group having from 1 to 5 carbon atoms in each alkyl chain, a (C1-C4)alkoxy group, a hydroxy group, a morpholino group, a N-methylpiperazino group, a hydroxyethylamino group, or a methylamino group, R9 represents a hydrogen atom or a hydroxyethyl group, or, when R8 represents a phenyl group, represents a straight chain or branched chain (C1-C5)alkyl group, or R8 and R9 together represent one of the following groups:: -N=CH-N=CH-, -CH2CH2OCH2CH2-, -CH2CH2CH2CH2-,

Y represents a (C1-C18)alkyl group, a phenyl group which may be unsubstituted or substituted by one or more of the same or different substituents selected from (C1-C3)alkyl groups, chlorine atoms, trifluoromethyl groups and nitro groups or which may be benzoannellated or a (C5-C8)cycloalkyl group, and Y represents a hydrogen atom or, when Y represents a (C1-C4)alkyl group, a (C1-C4)alkyl group,

3. A salt of a compound as claimed in claim 1 or claim 2.

4. A compound as claimed in claim 1, claim 2 or claim 3, which is specified in any one of Examples 1 to 133 herein.

5. A process for the preparation of a compound as claimed in claim 1, which comprises (a) reacting a compound of the general formula (II)

in which R1 to Re are defined as in claim 1, with an equimolar amount of a mercaptan of the general formula R7-SH, in which R7 is defined as in claim 1, or an equimolar to twofold equimolar amount of an amine of the general formula (IV)

in which R7, RB and R9 are defined as in claim 1, to give the hydrochloride and, if desired, converting the hydrochloride into a free base, or (b) reacting a compound of the general formula (I) given in claim 1, wherein A represents the group -SR7 wherein R7 represents a p-hydroxyethyl group, a p-hydroxypropyl group or a y-hydroxypropyl group, or the group

wherein R9 represents a hydrogen atom and R8 represents a p-hydroxyethyi group, a p-hydroxypropyl group or a y-hydroxypropyl group, with an equimolar amount of an isocyanate of the general formula Y--N=C=O wherein Y is as defined in claim 1, or with an equivalent amount of a dialkylcarbamic acid chloride of the formula (VI)

wherein both Y and Y' represent a (C1-C4)alkyl group, and, if desired, converting an acid group to a salt group, a base group to a salt group, or a salt group to an acid or base group or to another salt group.

6. A process as claimed in claim 5, wherein process (a) is carried out at a temperature in the range of from 50 to 2000C.

7. A process as claimed in claim 6, wherein the reaction with the mercaptan is carried out at a temperature in the range of from 50 to 1 500C.

8. A process as claimed in claim 6, wherein the reaction with the amine is carried out at a temperature in the range of from 130 to 2000 C.

9. A process as claimed in any one of claims 5 to 8, wherein the reaction of process (a) is carried out in an inert non polar solvent and wherein the halogen compound is added first and the nucleophilic compound is added later at an elevated temperature.

10. A process as claimed in any one of claims 5 to 9, wherein catalytic amounts of ammonium chloride are used in process (a).

11. A process as claimed in claim 5. wherein the reaction of process (b) is carried out in the presence of a base.

12. A process as claimed in claim 1 wherein the reaction with an isocyanate of the general formula (V) is carried out in the presence of catalytic amounts of a base.

1 3. A process as claimed in claim 11 wherein the reaction with an isocyanate of the general formula (VI) is carried out in the presence of an equimolar amount of a base.

14. A process as ciaimed in any one of claims 11 to 13, wherein process (b) is carried out at a temperature in the range of from 20 to 1 500C.

15. A process as claimed in claim 14, wherein process (b) is carried out at a temperature in the range of from 40 to 1400C.

1 6. A process as claimed in claim 5, which is carried out substantially as described in the Examples herein.

17. A compound as claimed in claim 1, whenever prepared by a process as claimed in any one of claims 5 to 16.

18. A salt of a compound claimed in claim 3, whenever prepared by a process as claimed in any one of claims 5 to 16.

19. A biocidal preparation which comprises a compound as claimed in any one of claims 1 to 4, 1 7 and 18 in admixture or conjunction with a suitable carrier.

20. A biocidai preparation as claimed in claim 19, which is in the form of a dust, a wettable powder, a dispersion or an emulsifiable concentrate.

21. A biocidal preparation as claimed in claim 19 or claim 20, which contains in the rangeof from 10 to 90% by weight of active ingredient.

22. A biocidal preparation as dlaimed in claim 19, which is substantially as described in the Examples herein.

23. A method of combating or controlling a fungal and/or bacterial and/or algal growth which comprises applying a compound as claimed in any one of claims 1 to 4, 17 and 1 8 or a e preparation as claimed in any one of claims 1 9 to 22 to the fungal and/br bacterial and/or algal growth or to the locus thereof or to a substrate infested with or liable to infestation by a fungal and/or bacterial and/or algal growth.

24. A process as claimed in claim 23, which is carried out substantially as described in the Examples herein.

25. A substrate whenever treated by a process as claimed in claim 23 or claim 24.

26. A fungal and/or bacterial and/or algal growth whenever controlled by a process as claimed in claim 23 or claim 24.