Europaisches Paten tamt J European Patent Office C11) Publication number: 0 128 006 B1 Office europeen des brevets

EUROPEAN PATENT SPECIFICATION

© Date of publication of patent specification: 18.09.91 © Int. Cl.5: C07C 211/39, C07C 229/38, C07C 249/02, C07C 255/24, © Application number: 84303640.1 C07C 257/00, C07C 233/00, C07D 227/00, C07D 307/68, @©r\n* Date of,«■ filing:f,,,ng: 30.05.84onnco, ^ ^ £ ^ ^^ C07D 251/40

A soil-disease-controlling agent.

® Priority: 31.05.83 JP 97545/83 03.06.83 JP 99959/83 (73) Proprietor: SUMITOMO CHEMICAL COMPANY, 17.08.83 JP 150853/83 LIMITED 18.08.83 JP 151117/83 Kitahama 4-chome 5-33 13.06.83 JP 106233/83 Chuo-ku Osaka 541 (JP) 09.06.83 JP 103949/83 @ Inventor: Tomioka, Hiroki © Date of publication of application: 2-14-7, Mefu 12.12.84 Bulletin 84/50 Takarazuka Hyogo-ken(JP) Inventor: Ooishi, Tadashi © Publication of the grant of the patent: 2-10-2-231, Sonehigashimachi 18.09.91 Bulletin 91/38 Toyonaka Osaka-fu(JP) Inventor: Takahashi, Junya ® Designated Contracting States: 4-2-303, Ryodocho CH DE FR GB IT LI NL Nishinomiya Hyogo-ken(JP) Inventor: Sasaki, Mitsuru References cited: 2-10-1-112, Sonehigashimachi CO DE-A- 1 956 285 GB-A- 806 798 Toyonaka Osaka-fu(JP) CO GB-A- 2 061 913 US-A- 2 512 293 Inventor: Hirata, Naonori o US-A- 3 385 846 US-A- 3 494 105 704-2, 7-510 Kanaokacho o US-A- 3 574 746 US-A- 3 679 699 Sakai Osaka-fu(JP) 00 US-A- 4 204 997

Note: Within nine months from the publication of the mention of the grant of the European patent, any person notice the Patent Office of the CL may give to European opposition to European patent granted. Notice of opposition LU shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid (Art. 99(1) European patent convention). Rank Xerox (UK) Business Services EP 0 128 006 B1

JOURNAL OF ORGANIC CHEMISTRY, vol. 35, no.6, 1970, pages 1861-1866; Washington, US. Representative: Pennant, Pyers et al KUO et al.: "Titanium chloride catalyzed ad- Stevens, Hewlett & Perkins 1 Serjeants' Inn dition of aziridine to ketones. A route to Fleet Street N-aziridinylenamines." London EC4Y1LL(GB)

JOURNAL OF THE CHEMICAL SOCIETY PER- KIN J:, 1980, pages 1960-1964; London, GB. M.G. BARLOW et al.: "Polyfluoroalkyl deriva- tives of nitrogen. Part. 49.ENE reactions of trifluoronitrosomethane: Formation of N- trif luoromethylhydroxylamines. "

CHEMICAL ABSTRACTS, vol. 88, nr.23, June 5, 1978, page 570, ref.nr.169910z;Columbus, Ohio, US . K.KUBO et al.: "Studies on N- cyclohexylanthranilic acid analogos. I.Synthesis and analgesic activity. "& Yamanouchi Seiyaku Kenkyu Hokoku, 1974 (pub. 1977),3, 8-12.

CHEMICAL ABSTRACTS, vo.. 86, nr. 13, March 28, 1977, page 54o, ref. nr. 89766a; Columbus, Ohio, US U.M. Dzhemnilev et al.: "Reaction of secondary amines with cyclic 1,3-dienes catalyzed by nickel complexes."

CHEMICAL ABSTRACTS; VOL. 81, NR. 17, OC- TOBER 28, 1974, PAGE 522, REF. NR.1 05396 J;COLUMBUS, OHIO, US. G.S. CHEKRII ET AL: "CYCLIZATION OF 2-R-AMINO DERIVATIVES OF 2-THIAZOLINE."

HELVETICA CHIMICA ACTA, vol. 62, Fasc. 7,nr.219, 1979, pages 2129-2153; Basel, CH. M.MARKY et al.: "Photoreaktionen von 1-Alkylbenztriazolen."

JOURNAL OF ORGANIC CHEMISTRY; vol. 45, 1980, pages 2709-2710; Washington, US. R. ODLE et al.: "Conversion of 2 halo- N-allylamines to indoles via palladium ( = ) oxidative addition-insertion reactions."

CHEMICAL ABSTRACTS, vol. 63, nr. 7, Sep- tember 27, 1965, column 8765a; Columbus, Ohio, US. R.M.GIPSON et al.: "Relation of structure to biological activity of some un- saturated derivatives of cyclopen- taneglycine." EP 0 128 006 B1

TETRAHEDRON, vol. 37, nr. 23, 1981, pages 4007-4016; Oxford, GB, G.E. KECK et al.: "A versatile method for carbon-nitrogen bond formation via ene reactions of acylnitroso compounds."

TETRAHEDRON LETTERS, vol. 23, nr. 5o, 1982, pages 5315-5318, Oxford, GB.MIWAKO MORI et al.: "Cyclization of alpha-haloamide with internal double bond by use of the low-valent metal complex."

CHEMICAL ABSTRACTS, vol. 91, nr. 23, De- cember 3, 1979, page 624, ref. nr. 193o91r; Columbus, Ohio, US. E. SCHMITZ et al.: "Synthesis of heterocyclic compounds by carbon-carbon bond closure.lll. Syntheses of heterocyclic compounds by in- tramolecular ene reaction."

TETRAHEDRON LETTERS, nr. 41, 1966, pages 5061-5065, Pergamon Press Ltd, Oxford, GB H.ZIMMER et al.: "Die Photolyse von Triphenylphosphin-t-Butylimin"

JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 17, June 1980, pages 753-758; R.B.MOFFETT.: "Analogs of heterocyclic CNS agents."

HELVETICA CHIMICA ACTA, vol. 56, Fasc. nr. 183, 1973, pages 1807-1812; Basel, CH. W.OPPOLZER et al.: "A new stereoselective approach to substituted pyrrolidines by in- tramolecular enereactions."

JOURNAL OF ORGANIC CHEMISTRY, vol. 33, nr. 5, May 1968, pages 1844-1846, Washing- ton, US A.M.WEIDLER-KUBANEK et al.: "Addition of hexafluoroacetone to ketenimines."

CHEMICAL ABSTRACTS, vol. 84, nr. 21, May 24, 1976, page 535, ref. nr. 150500m; Colum- bus, Ohio, US DD-A-113 903 (E. SCHMITZ et al.) 05-07-1975

JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 5, June 1968, pages 419-421; P.E.FANTA et al.: "Aziridines. XVII. Reactions of 6-azabicyclo (3.1.0) hexane (1)." EP 0 128 006 B1

JOURNAL OF THE AMERICAN CHEMICAL SO- CIETY, vol. 93, nr. 15, July 1971, pages 3833-3834; Washington, US W. OPPOLZER: "Intramolecular cycloadditions of o- quinodimethanes."

CHEMICAL ABSTRACTS, vol. 90, nr. 7, Feb- ruary 12, 1979, page 107, ref. nr.49009g; Co- lumbus, Ohio, US E.G.DELEGAN et al.: "Antimicrobial activity of some 5-R-3-alkenyl-2-thiohydantoins and products of their cyclization."

CHEMICAL ABSTRACTS, vol. 78, nr. 25, June 25, 1973, page 408, ref. nr.159509e; Colum- bus, Ohio, US T.A. KRASNITSKAYA et al.: "Cyclization of substituded N- allylpseudothiohydantoins and N- allylpseudothiohydantoic acids."

JOURNAL OF THE CHEMICAL SOCIETY PER- KIN J. 1980, pages 2383-2388; London, GB Md, GIASUDDIN AHMED et al.: "Enamine chemistry. Part 27. The effect of additional alpha- and beta-hetero-atoms on the ppi- conjugation and reactivity of enamines. Sub- or super-enamines?"

CHEMICAL ABSTRACTS, vol. 98, nr. 5, Janu- ary 31, 1983, page 638, ref. nr. 34457t; Colum- bus, Ohio, US E. SCHMITZ et al.: "Synthesis of heterocyclic compounds by carbon- carbon bond closure. IV. Synthesis of heterocyclic compounds by intramolecular diene reaction."

CHEMICAL ABSTRACTS, VOL. 101, NR. 15, OCTOBER 8, 1984, PAGE 685, REF. NR. 130435K; COLUMBUS, OHIO, US EP 0 128 006 B1

Description

The present invention relates to a 2-cycloalkenylamine derivative and its salt which are soil disease- controlling agents, and production thereof. The 2-cycloalkenylamine derivative and its salt which are the 5 active ingredient of the present invention, have excellent controlling effect against soil diseases caused by plant pathogens. More particularly, the present invention relates to a soil disease-controlling agent contain- ing as an active ingredient a 2-cycloalkenylamine derivative or its salt (hereinafter referred to as present compound), a novel 2-cycloalkenylamine derivative and its salt, and production thereof, said 2-cycloal- kenylamine derivative being represented by the formula (I), 10

^Vn / XR2 75

wherein R1 represents a hydrogen atom, a hydroxy, amino, lower cycloalkyl, lower cycloalkenyl, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, arylcarbonyloxy or aryl group, a lower alkyl group which may 20 be substituted with a halogen atom or a cyano, nitro, hydroxy, lower alkoxy, lower cycloalkyl, aryl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, or a lower alkoxyl group which may be substituted with an aryl group, R2 represents a hydrogen atom, a hydroxy, amino, lower cycloalkyl, lower cycloalkenyl, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, arylcarbonyloxy or 25 aryl group, a lower alkyl group which may be substituted with a halogen atom or a cyano, nitro, hydroxy, lower alkoxy, lower cycloalkyl, aryl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycar- bonyl, lower alkylcarbonyl or dialkylamino group a lower alkenyl group which may be substituted with a halogen atom or an aryl group, a lower alkoxyl group which may be substituted with an aryl group, or a group represented by the formula, 30 -C-R3 II X

35 wherein R3 represents a hydrogen atom, a lower alkynyl, cycloalkyl, cycloalkenyl, aryl, lower alkyl- substituted oxathiinyl, uracilyl, arylcarbonyl or benzdioxanyl group, an alkyl group which may be substituted with a halogen atom or a lower alkoxy, cycloalkoxy, aryl, aryloxy, arylthio, cyano, carboxy or lower alkoxycarbonyl group, or a lower alkenyl group which may be substituted with a halogen atom or a carboxy 40 lower alkoxy or alkoxycarbonyl group, and X represents an oxygen or sulfur atom or an imino group, or R3 and R1, taken together, may form a lower alkylene or o-phenylene group, or R1 and R2, taken together, may form an alkylene or alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group or an imino group or at least one of substituents, a group represented by the formula,

45 -c - z - c- II II X Y so wherein X and Y, which may be the same or different, represent an oxygen or sulfur atom or an imino group, and Z represents a cycloalkylene, cycloalkenylene, bicycloalkylene or arylene group, a lower alkylene group which may be substituted with a hydroxy, lower alkoxy, aryl, lower alkylcarbonyloxy, methylene, alkylidene, mercapto, arylcarbamoyloxy which may be substituted, or lower alkylcarbonylthio group, a lower alkenylene group which may be substituted with a halogen atom or a carboxy or aryl group, 55 or a substituent represented by the formula -A - R- (in which A represents an oxygen or sulfur atom or an imino group, and R represents a lower alkylene group), or a substituted alkylidene group represented by the formula, EP 0 128 006 B1

■<;

5

wherein R4 and Rs, which may be the same or different, represent a hydrogen atom, a nitro, lower cycloalkyl, aryl, dihydropyranyl, carboxy or acyl group, a lower alkyl group which may be substituted with a halogen atom or a hydroxy, lower alkoxy, aryloxy, lower alkoxycarbonyl, di-lower alkylamino, acyl or aryl w group, a lower alkenyl group which may be substituted with a halogen atom or a hydroxy or aryl group, or a lower alkynyl group which may be substituted with an aryl group, or R* and R5, taken together, may form an alkylene or alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group or an imino group, and n represents 1 , 2, 3 or 4 and an inert carrier. 75 According to a further aspect, the present invention provides 2-cycloalkenylamines having the formula:

««*>»

25 wherein R2 represents amino, C3 alkynyl, C2-3 alkoxycarbonyl-substituted phenylthio, phenylthio or phenyl- carbonyloxy group, a C1 -5 alkyl group which is substituted with a halogen atom or a cyano, C1 -2 alkoxy, C2-3 alkoxycarbonyl, or acetyl group, or a C1-2 alkoxy group which may be substituted with a phenyl group, and n represents 2 or 3. and 30

H , 35 (CHJ ■/Y

40 wherein R3 represents a hydrogen atom, Ce cycloalkenyl, benzoyl, benzodioxanyl, thienyl, pyridyl, quinox- alyl, 3-methylbenzofuryl, naphthyl group or

45 P

a C1-13 alkyl group which may be substituted with a halogen atom, carboxy, phenyl, 3,4-ethylenediox- 50 yphenyl, halogen-substituted phenyl, imidazolyl, triazolyl group, C1-4 alkoxy, halogen-substituted phenoxy, methyl-substituted phenyl, cyano, C2-3 alkoxycarbonyl, phenylthio or C3-10 cycloalkoxy group, a phenyl group which may be substituted with a halogen atom, hydroxy, nitro, carboxy, C1-2 alkoxy, phenoxy, C1-4. alkyl, cyano, C2-4. dialkylamino or C1 haloalkyl group, a C2-3 alkenyl group which may be substituted with a halogen atom, carboxy, C2-+ alkoxycarbonyl, 55 EP 0 128 006 B1

T-O

or C1-2 alkoxy group, a C3-6 cycloalkyl group which may be substituted with carboxy, methyl, dichlorovinyl or phenyl group, a furyl group which may be substituted with a methyl group, a pyrolyl group which may be substituted with a methyl group, X represents an oxygen or sulfur atom, and n represents 2 or 3, provided that the following combinations of n and R3 are excluded: 10 n = 2 and R3 = methyl, propyl, phenyl, chloromethyl, trichloromethyl, tert-butyl or trifluoromethyl; n = 3 and R3 = methyl or trifluoromethyl group, and

75

20

wherein X and Y, which may be the same or different, represent an oxygen or sulfur atom, Z represents a C3-6cycloalkylene, C6 cycloalkenylene, C6-7 bicycloalkylene pyridylene group, phenylene group which is 25 substituted with a halogen atom or nitro group, C2-3 alkylene group which may be substituted with a hydroxy, C1-2 alkoxy, phenyl, acetoxy, C2-3 alkylidene, mercapto, phenylcarbamoyloxy or acetylthio group, a C2 alkenylene group which may be substituted with a halogen atom or phenyl group, or a substituent represented by the formula -A-R-(in which A represents an oxygen or sulfur atom or an imino group, and R represents a C1 -3 alkylene group), and n represents 2 or 3. 30

35

wherein R* and R5, which may be the same or different, represent a hydrogen atom, a nitro, lower 40 cycloalkyl, aryl, dihydropyranyl, carboxy or acyl group, a lower alkyl group which may be substituted with a halogen atom or a hydroxy, lower alkoxy, aryloxy, lower alkoxycarbonyl, di-lower alkylamino, acyl or aryl group, a lower alkenyl group which may be substituted with a halogen atom or a hydroxy or aryl group, or a lower alkynyl group which may be substituted with an aryl group, or R* and R5, taken together, may form an alkylene or alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group or an imino 45 group, and n represents 1, 2, 3 or 4, provided that the following cases are excluded: when n is 1, R* is a butyl group and R5 is a hexyl group, or R4 and R5, taken together, form a 2,4,4-trimethyl-1-pentenylene group; and when n is 2, R4 and R5, taken together, form a pentylene group. The present inventors have made an extensive study on controlling agents for soil diseases, one of the plant diseases which are most difficult to control, and as a result, found that the present compound has 50 excellent controlling effect on soil diseases caused by many plant pathogens. In the plant pathogens on which the present compound has excellent controlling effect, there are included pathogens belonging to genus Fusarium such as Fusarium oxysporum f. sp. licopersici (fusarium wilt of tomato), Fusarium oxysporum f. sp. raphani (yellows of Japanese radish), Fusarium oxysporum f. sp. cucumerinum (fusarium wilt of cucumber), Fusarium oxysporum f. sp. niveum (fusarium wilt of water- 55 melon), Fusarium oxysporum f. sp. conglutinans (yellows of cabbage), Fusarium oxysporum f. sp. fragariae (yellows of strawberry), Fusarium nivale f. sp. graminicola (fusarium snow blight of wheat), Fusarium roseum f. sp. cerealis (fusarium blight of wheat), Fusarium solani f. sp. pisi (root rot of pea) and Fusarium oxysporum f. sp. vasinfectum (fusarium wilt of cotton), pathogens belonging to genus Pythium such as EP 0 128 006 B1

Pythium aphanidermatum (damping-off of cucumber) and Pythium debaryanum (damping-off of tobacco), pathogens belonging to genus Rhizoctonia such as Rhizoctonia solani (damping-off of cucumber, black scurf of potato, root rot of sugar beet, rhizoctonia rot of zoysia grass, sore shin of tobacco), Rhizoctonia Candida (damping-off of sugar beet) and Rhizoctonia bataticola (charcoal rot of soybean), pathogens 5 belonging to genus Verticillium such as Verticillium alboatrum (verticillium wilt of eggplant and verticillium wilt of Chinese cabbage) and Verticillium dahliae (verticillium wilt of udo), pathogens belonging to genus Corticium such as Corticium rolfsii (southern blight of kidney bean), pathogens belonging to genus Typhula such as Typhula incamata and Typhula ishikariensis (typhula snow blight of wheat, typhula snow blight of alfalfa) w and pathogens belonging to genus Plasmodiophora such as plasmodiophora brassicae (clubroot of Chinese cabbage, clubroot of cabbage), and the like. The present compound, therefore, can be used as the active ingredient of soil disease-controlling agents for plowland, paddy field, orchard, tea garden, mulberry field, pasture, turf and the like. In the foregoing formula (I) representing the present compound, the aryl group includes for example a 75 phenyl, naphthyl, biphenyl, imidazolyl, triazolyl, pyrazolyl, thiazolyl, benzothiazolyl, triazinyl, pyrazinyl, pyrimidyl, uracilyl, furyl, pyridyl, quinolyl, pyrrolyl, quinoxalyl, benzimidazolyl, benzofuryl and thienyl groups, all of which may have a substituent. Specifically, there are given for example a phenyl, halogen- substituted phenyl, lower alkylphenyl, lower alkenylphenyl, lower haloalkylphenyl, nitrophenyl, cyanophenyl, carboxyphenyl, naphthyl, lower thioalkoxyphenyl, lower alkoxyphenyl, hydroxyphenyl, biphenyl, arylox- 20 yphenyl, aryl-substituted alkoxyphenyl, formylphenyl, hydroxynaphthyl, nitronaphthyl, halobiphenyl, quinox- alyl, thienyl, lower alkylthienyl, lower alkoxycarbonylphenyl, benzoylphenyl, aryl-substituted lower alkox- yphenyl, di-lower alkylaminophenyl, lower acylaminophenyl, lower acylphenyl, imidazolyl, triazolyl, car- bamoylphenyl, arylazophenyl, pyrazolyl, arylpyrazolyl, thiazolyl, benzothiazolyl, halothiazolyl, nitrothiazolyl, lower alkylthiazolyl, lower haloalkylthiazolyl, lower alkylbenzothiazolyl, arylthiazolyl, lower alkoxyben- 25 zothiazolyl, arylsulfonylthiazolyl, triazinyl, halotriazinyl, lower alkyltriazinyl, lower cycloalkenylaminotriazinyl, pyrazinyl, carboxypyrazinyl, pyrimidyl, halopyrimidyl, lower alkylpyrimidyl, halogenated lower alkylpyrimidyl, hydroxypyrimidyl, lower alkylthiopyrimidyl, uracilyl, furyl, benzofuryl, lower alkylbenzofuryl, lower alkylfuryl, lower haloalkylpyridyl, halopyridyl, lower alkylpyridyl, aryl lower alkoxypyridyl, hydroxypyridyl, nitropyridyl, pyridyl, lower alkylquinolyl, quinolyl, lower alkoxyquinolyl, pyrrolyl and N-lower alkylpyrrolyl groups, and the 30 like. In the foregoing formula (I) representing the present compound, the arylene group includes for example an o-phenylene and naphthylene groups and groups described below, all of which may be substituted with a halogen atom or a nitro or carboxyl group :

35

40 Next, a method for producing the present compound will be illustrated.

Method (a) :

45 When the present compound is an amine compound represented by the formula (II),

6 €>< (ID (CH ) / "\ 8Q 50 "L n/ K

wherein R6 represents a hydrogen atom, a hydroxy, amino, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, arylcarbonyloxy or aryl group, a lower alkyl group which is substituted with a halogen atom or a 55 cyano, nitro, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which is substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, R8 represents a lower alkynyl, tetrahydrofurfuryl, piperidyl, arylcarbonyloxy or arylthio group, a lower alkyl group which is

8 EP 0 128 006 B1

substituted with a halogen atom or a cyano, nitro, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, lower alkylcarbonyl, dialkylamino or aryloxycarbonyl group, a lower alkenyl group which is substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, and n represents the same meaning as above,* it can be produced, for example, by reacting a compound represented by the formula (III),

icL). >NHR {III)

wherein Re and n represent the same meanings as above, 75 with the equivalent of a compound represented by the formula (IV),

L - R8 (IV)

wherein R8 represents the same meaning as above, and L represents a halogen atom, an arylcarbonyloxy, 20 hydroxy or lower alkylsulfonyloxy group, or a benzenesulfonyloxy group which may be substituted with a lower alkyl group, at 0° to 150° C for 1 to 24 hours with or without a solvent in the presence or absence of the equivalent of an acid-binding agent. As the compound represented by the formula (IV), there are given for example methyl iodide, ethyl 25 iodide, 1-bromopropane, 2-bromopropane, 1-bromobutane, 1-bromo-2-methylpropane, 1-bromopentane, 1- bromo-3-methylbutane, 1-iodohexane, 1-bromoheptane, 2-bromo-5-ethylnonane, 3-bromopropionitrile, cyclopropylmethyl bromide, cyclohexyl bromide, 1-bromo-4-methylcyclohexane, cyclohexylmethyl bromide, 2,3,5-trimethylcyclohexylmethyl bromide, cyclopentyl bromide, tert-butyl bromide, cyclopropyl bromide, dibromomethane, diiodomethane, bromochloromethane, chlorodifluoromethane, bromotrichloromethane, 30 tribromomethane, tetrabromomethane, 1-bromo-2-chloroethane, 1 ,2-dibromoethane, 1,1,1-trichloroethane, pentachloroethane, hexachloroethane, 1,1-dibromoethane, ethylene chlorohydrin, 2,2-dibromoethane, eth- ylene bromohydrin, 2,2-dichloroethanol, 2,2,2-trifluoroethanol, 1 ,2-dibromopropane, 1 ,3-dibromopropane, 1- bromo-3-chloropropane, 1 ,2,3-tribromopropane, 1 ,2-dibromobutane, 1 ,4-dibromobutane, 2,3-dibromobutane, 1-bromo-3-chloro-2-methylpropane, 1 ,5-dibromopentane, 1 ,6-dibromohexane, 1 ,3-dibromobutane, 2-iodo- 35 1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane, 1,1-dichloroethane, allyl bromide, 3-bromocycloheptene, 3- bromocyclooctene, 3-bromocyclohexene, 3-bromocyclopentene, propargyl bromide, methallyl chloride, 1- chloro-2-butene, 3-chloro-1-butene, 4-bromo-1-butene, 3-hexenyl bromide, 1,3-dichloro-1-propene, 2,3- dichloro-1-propene, 1 ,2,3-trichloropropene, 1,3-dichloro-2-butene, 1 ,4-dichloro-2-butene, cinnamyl chloride, bicyclo[2.2.1]-3-methylheptenylmethyl bromide, benzyl bromide, p-chlorobenzyl chloride, m-bromobenzyl 40 bromide, o-fluorobenzyl bromide, 2,4-dichlorobenzyl chloride, p-methylbenzyl chloride, p-ethylbenzyl chlo- ride, p-isopropylbenzyl chloride, p-tert-butylbenzyl bromide, vinylbenzyl chloride, 2,5-dimethylbenzyl chlo- ride, m-trifluoromethylbenzyl chloride, m-nitrobenzyl bromide, m-cyanobenzyl bromide, a,a'-dichloro-p- xylene, a,a'-dibromo-o-xylene, a-chloroethylbenzene, p-bromomethylbenzoic acid, phenethyl bromide, p- nitrophenethyl bromide, i3-bromopropylbenzene, 0-bromoisopropylbenzene, a,^-dibromoethylbenzene, 45 diphenylmethyl bromide, triphenylmethyl bromide, 2-chloro-4-nitrobenzyl chloride, 1-chloromethylnaph- thalene, p-methoxybenzyl chloride, p-methylphenyl-n-butyl bromide, 2,4-dimethylphenethyl bromide, phenyl-n-butyl bromide, phenyl-n-propyl bromide, ethyl bromoacetate, methyl bromoacetate, isopropyl chloroacetate, n-butyl chloroacetate, phenyl chloroacetate, allyl chloroacetate, vinyl chloroacetate, methyl 2- chloropropionate, ethyl 2-bromopropionate, ethyl 2-bromopropionate, ethyl 2-bromobutyrate, ethyl 2- 50 bromoisobutyrate, lactonitrile, hydroxyacetonitrile, acetone cyanhydrin, 2,6-dichloro-4-methylpyrimidine, 4- bromobutyronitrile, 5-bromovaleronitrile, 2-chloropropionitrile, chloroacetonitrile, bromoacetic acid, 2- chloropropionic acid, 2-bromo-n-butyric acid, a-bromoisobutyric acid, 2-bromoisovaleric acid, cyanuric chloride, 6-chloro-3-trifluoromethylpyridine, 5,6-dichloro-3-trifluoromethylpyridine, diethyl chlorosuccinate, 1 ,3-cyclohexanedione, phenylsulfenyl bromide, 2-methoxycarbonylphenylsulfenyl bromide, bromoacetone, 55 benzoyl peroxide, 2-bromomethylbicyclo[2.2.1]heptane and the like.

Method (b) : EP 0 128 006 B1

When the present compound is an amine compound represented by the formula (V),

i >— N/ (V)

w wherein R6 and n represent the same meanings as above, and R7 represents a hydrogen atom, a hydroxy, amino, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio or arylcarbonyloxy group, a lower alkyl group which is substituted with a halogen atom or a cyano, nitro, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which is substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be 15 substituted with an aryl group, or RG and R7, taken together, may form alkylene or alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group, an amino group or at least one of substituents provided that a case wherein R5 and R7 are a hydrogen atom at the same time is excluded, it can be produced, for example, by reacting an amine represented by the formula (VI),

20 R6 ^>H (VI) R^

25 wherein Rs and R7 represent the same meanings as above, with 0.5 to 1 equivalent of a compound represented by the formula (VII),

30

(Ct� "E (VII)

35 wherein n represents the same meaning as above, and E represents a halogen atom, a lower alkylsul- fonyloxy group or a benzenesulfonyloxy group which may be substituted with a lower alkyl group, with or without a solvent for 1 to 24 hours in the presence or absence of not less than the equivalent of an acid-binding agent. 40 As the compound represented by the formula (VI), there are given for example hydrazine, methylamine, ethylamine, n-propylamine, isopropylamine, n-amylamine, 2-ethylhexylamine, n-butylamine, isobutylamine, sec-butylamine, tert-butylamine, 2-methylalIylamine, 3-cyclohexenylamine, allylamine, vinylamine, isoamylamine, neopentylamine, 1 ,2-dimethylpropylamine, n-hexylamine, n-heptylamine, 2-methylpen- tylamine, 1 ,3,3-tetramethylbutylamine, cyclopropylamine, cyclopentylamine, 3-methylcyclohexylamine, 45 cyclohexylamine, 1,1-dimethylpropargylamine, 1,1-diethylpropargylamine, ethylpropargylamine, 2- chloroethylamine, 2-bromoethylamine, 3-bromopropylamine, 2,2,2-trifluoroethylamine, 2-methoxyethylamine, 2-ethoxyethylamine, aminoacetaldehyde dimethyl acetal, aminoacetaldehyde diethyl acetal, 3-methox- ypropylamine, 3-ethoxypropylamine, 3-isopropoxypropylamine, butoxypropylamine, isobutoxypropylamine, 2-ethylhexyloxypropylamine, /3-aminopropionitrile, cyclopropylmethylamine, cyclohexylmethylamine, N-(2- 50 ethylhexyl)-2-cyclopentenylamine, dimethylamine, diethylamine, di-n-propylamine, di-(2-ethylhexyl)amine, N-methylcyclohexylamine, diallylamine, di-n-butylamine, diisobutylamine, di-sec-butylamine, di-n- amylamine, diisoamylamine, di-n-hexylamine, dicyclohexylamine, N-methylpropargylamine, N-ethyl-n- butylamine, N-methyl-^-alanylnitrile, /8-aminoethanol, diisopropanolamine, isopropylcyclohexylamine, diisopropylamine, ethylbutylamine, N-(2-chloroethyl)methylamine, N-methylethanolamine, 2- 55 ethylaminoethanol, 2-isopropylaminoethanol, 2-tert-butylaminoethanol, diethanolamine, N-(/3-hydroxyethyl)-2- cyclopentenylamine, tris(oxymethyl)aminomethane, 1-hydroxyethylamine, 3-amino-1-propanol, 2-amino-1- propanol, 1-amino-2-propanol, 2-amino-1-butanol, diglycolamine, 5-amino-1-pentanol, 6-amino-1-hexanol, 3- amino-1 ,2-propanediol, 1 -aminomethyl-1 -cyclohexanol, N-phenylethanolamine, 2-benzylamino-1 -propanol,

10 EP 0 128 006 B1

N-n-butylethanolamine, 3-aminomethyl-3,5,5-trimethylcyclohexano[, benzylamine, 4-chlorobenzylamine, 4- methoxybenzylamine, 2,4-dichlorobenzylamine, N-methylbenzylamine, dibenzylamine, aminodiphenyl- methane, a-methylbenzylamine, N-isopropylbenzylamine, 4-hydroxy-3-methoxybenzylamine, m-nitroben- zylamine, 2-methylbenzylamine, a-phenethylamine, phenethylamine, p-chlorophenethylamine, 4- 5 bromophenylbutylamine, N-ethylbenzylamine, aniline, o-hydroxyaniline, o-nitroaniline, 3-nitro-4- aminotoluene, 2-chloro-4-nitroaniline, 4-methoxy-2-nitroaniline, 2-fluoro-5-nitroaniline, N-methyl-p-nitroaniline, p-n-butylaniline, o-phenylaniline, 3,4-dimethylaniline, 2,4,6-trimethylaniline, m-bromoaniline, o-fluoroaniline, 2,5-dichloroaniline, 3,5-dichloroaniline, 2,4,5-trichloroaniline, 2-chloro-6-methylaniline, 5-chloro-2-hydrox- yaniline, 3-methoxy-6-chloroaniline, 3-trifluoromethyl-4-chloroaniline, 2-nitro-4-trifluoromethylaniline, 4- 10 trifluoromethylaniline, 2-trifluoromethylaniline, 4-methoxy-3-trifluoromethylaniline, 2,4-dinitroaniline, 2-bromo- 4,6-dinitroaniline, 3-cyano-4-chloroaniline, o-methoxyaniline, 4-methoxy-2-methylaniline, 2,5-dimethox- yaniline, 3,4,5-trimethoxyaniline, 3,4-dimethylenedioxyaniline, 6-amino-1 ,4-benzdioxane, p-phenoxyaniline, 2,4-dibenzyloxyaniline, 4-benzyloxyaniline, p-cresidine, N-ethylaniline, N-methoxy-o-toluidine, diphenylamine, N-methyl-p-nitroaniline, N-ethyl-o-toluidine, N-methyl-p-anisidine, N-benzyl-p-anisidine, 8- 75 amino-2-naphthol, 4-nitro-1-naphthylamine, 5,6,7,8-tetrahydro-1-naphthylamine, 1 ,2,3,4-tetrahydronaph- thylamine, a-naphthylamine, 4-(2,4,6-trichlorophenyl)aniline, 4,4'-oxydianiline, 3-methylthioaniline, 4- aminobenzonitrile, ethyl m-aminobenzoate, p-aminoazobenzene, 2-aminobenzophenone, 4-aminobenzamide, m-aminoacetophenone, 1 ,2,4-triazole, 4-amino-1 ,2,4-triazole, 3-amino-2-phenylpyrazole, 3,5-dimethyl- pyrazole, 2-aminothiazole, 2-aminobenzothiazole, 2-amino-5-chlorothiazole, 2-amino-5-nitrothiazole, 2-amino- 20 4-methylthiazole, 2-amino-5,6-dihydro-4H-cyclopentathiazole, 2-amino-(4-chloromethyl)thiazole, 2-amino-5(p- nitrophenylsulfonyl)thiazole, 2-amino-6-methoxybenzothiazole, 2-amino-6-methylbenzothiazole, 2-amino-4- phenylthiazole, benzimidazole, 2-benzimidazole methanol, 2-benzyl-2-imidazoline, 2-hydroxybenzimidazole, 2-methylthio-2-imidazoline, imidazole, 2-(1-naphthylmethyl)-2-imidazoline 2-ethylimidazole, 2- phenylimidazole, 4,5-dicyanoimidazole, 2,4,5-tribromoimidazole, 2-methyl-4,5-dicyanoimidazole, 4- 25 nitroimidazole, 5-chlorobenzimidazole, 2-(a-hydroxybenzyl)benzimidazole, 3-amino-1 ,2,4-triazine, 3-amino- 5,6-dimethyl-1 ,2,4-triazine, aminopyrazine, 3-aminopyrazine-2-carboxylic acid, 2-amino-4,6-dich- loropyrimidine, 2-aminopyrimidine, 2-amino-6-chloro-4-hydroxypyrimidine, 4-amino-6-chloro-2-methyl- thiopyrimidine, 5-aminouracil, furfurylamine, tetrahydrofurfurylamine, hydroxylamine, N-methylhydrox- ylamine, O-methylhydroxylamine, O-ethylhydroxylamine, O,N-dimethylhydroxylamine, o-benzyloxyamine, 2- 30 amino-5-bromopyridine, 6-amino-3-picoline, 2-amino-3-benzyloxypyridine, 2-amino-3-hydroxypyridine, 2- amino-5-nitropyridine, 2-aminopyridine, 2-aminomethylpyridine, 1 ,2,5,6-tetrahydropyridine, 8-amino-6- methylquinoline, 8-aminoquinoline, 3,5-diiodo-4-pyridone, 8-amino-6-methoxyquinoline, 1,2,3,4- tetrahydroquinoline, 1 ,2,3,4-tetrahydroisoquinoline, N-(3-aminopropyl)morpholine, 2,6-dimethylmorpholine, morpholine, thiomorpholine, 3-acetyl-2,4-dimethylpyrrole, 2,5-dimethylpyrrole, 2,5-dimethylpyrrolidine, pyr- 35 role, pyrrolidine, 3-pyrroline, methyl pyrrole-2-carboxylate, 3-pyrrolidinol, N-methylpiperazine, 1-(o-methox- yphenyl)piperazine, 1 -(2-pyridyl)piperazine, N-(a,a,a-trifluoromethyl-m-toly l)piperazine, ethyleneimine, dodecamethyleneimine, hexamethyleneimine, 3-amino-N-ethylpiperidine, 4-amino-1-benzylpiperidine, N-(2- aminoethyl)piperidine, 4-bromo-4-phenylpiperidine, 4-(p-chlorophenyl)-4-hydroxypiperidine, 4-cyano-4- phenylpiperidine, 2,6-dimethylpiperidine, piperidine, 2-piperidine ethanol, 2,2,6,6-tetramethyl-4-piperidone, 40 2,2,6,6-tetramethylpiperidine and the like. The solvent used in the above methods (a) and (b) includes for example aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, etc., aromatic hydrocarbons such as benzene, toluene, xylene, etc., halogenated hydrocarbons such as chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene, etc., ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, diethylene 45 glycol dimethyl ether, etc., nitro compounds such as nitroethane, nitrobenzene, etc., nitriles such as acetonitrile, isobutyronitrile, etc., tertiary amines such as pyridine, triethylamine, N,N-diethylaniline, tributylamine, N-methylmorpholine, etc., acid amides such as N,N-dimethylformamide, acetamide, etc., sulfur compounds such as dimethyl sulfoxide, sulfolane, etc., and mixtures thereof. Also, the acid-binding agent includes for example organic bases such as pyridine, triethylamine, N,N- 50 diethylaniline, etc., and inorganic bases such as sodium carbonate, potassium carbonate sodium hydride, etc. After completion of the reaction, the reaction solution is after-treated as usual, for example it is poured into water and the organic layer is separated and concentrated. If necessary, the product obtained is purified by chromatography, distillation, recrystallization and the like. 55 Next, examples of production of the present compound by the methods (a) and (b) will be shown.

Production example 1

11 EP 0 128 006 B1

To a mixture of 2-cyclohexenylamine (0.97 g, 10 mmoles), triethylamine (1.01 g, 10 mmoles) and chloroform (10 ml) was added dropwise ethyl bromoacetate (1.67 g, 10 mmoles) at 0° to 5°C. After completion of the addition, the resulting mixture was heated under reflux for 3 hours. Then the reaction solution was after-treated as usual and purified by chromatography to obtain 1 .28 g of N-(2-cyclohexenyl)glycine ethyl ester [Compound (1)].

n"-3 1.4711 10

Production example 2

J5 2-Cycloheptenylamine (1.11 g, 10 mmoles) was added dropwise to a mixture of an aqueous 50 wt.% hydroxyacetonitrile solution (1.14 g, 10 mmoles) and an aqueous 50% EtOH (10 ml) at 35° to 40°C. After the resulting mixture was kept at this temperature for 30 minutes, it was after-treated as usual and purified by chromatography to obtain 1 .35 g of N-(2-cycloheptenyl)glycinonitrile [Compound (2)].

20 24 0 n^4-U 1.4950

25 Production example 3

A mixture of 3-bromocycloheptene (1.75 g, 10 mmoles), triethylamine (1.01 g, 10 mmoles), morpholine (0.87 g, 10 mmoles) and chloroform (10 ml) was heated under reflux for 3 hours. After completion of the refluxing, the reaction mixture was after-treated as usual and purified by chromatog- 30 raphy to obtain 0.91 g of N-(2-cycloheptenyl)morpholine [Compound (3)].

n^5'2 1.5039

35 Some of the present compounds which can be produced by these methods are shown in Table 1 .

40

45

50

55

12 EP 0 128 006 B1

Table 1

Present compounds represented by the formula.

1 (CH

10 Compound R R n Physical No. constant

(1) H -CH2COOC2H5 2 no3*3 i-^ll 75 n24*0 (2) H -CH2CN 3 1.4950 n25 ' 2 (3) -CH2CH2OCH2CH2- 3 1.5039

3 n^6*2 1-4791 20 (4) H -C(CH3)2CN

(5) H -CH(CH3)CN 3 n^6'0 1.4813

(6) H -CH2COOCH3 3 ^'2 1.4811 25 n22'9 (7) H -CH2COOC2H5 3 1.4761 n22'0 (8) H -*». 3 1.5202

30 (9) H a », 3 m.p. 105°C -/ Vno

(10) H A 3 n25'5 1.4986 35

ni8'8 l'sin (ID h /=\ 2

40 (12) H -OCH3 2 nj°-2 1.4680 n26'7 (13) H Cl 3 l

45 NC1

Cont'd

50

55

13 EP 0 128 006 B1

Compound R R2 n Physical No. constant

(14) H - /r"\ 3 n26*6 1.5280

p

(15) H -CH2C=CH 3 n23*7 1.5030

10 (16) H v-\ 3 n22*7 1.5196

(17) H -CH(CH3)2 3 n^4'8 1-4702 2 75 (18) H -CH2COCH3 3 n*7 - 1.5375

(19) H -{CH2)5C1 3 n23"5 1.4990

(20) -CBr = NCBr = CBr- 2 n24'0 6041 ° 1 20 1 9 (21) -N = CCH3 - CH = CCH3- 3 n23 * 1.5189

(22) H -CH2COOH 3 m.p. >300aC (dec.)

25 (23) H -CHCH3COOCH3 3 n^2"3 1-4718 l (24) H -CH2CN 2 n20 ' 1.5231

(25) H -C2H5 2 n21'6 1.4781 30 n29*7 (26) H /r-A 2 1.5330 -OCH.-V } D -1 (27) H -CHCOOC2H5 2 n30 * 1.4640 35 CH2COOC2H5

(28) H ~OC2H5 2 n30'1 1.4629

(29) H j 1 2 Resinous product 40

(30) H n s\ 2 m.p. 82°-84°C

45 (31) H Cl 2 n29"5 1.5170

50 Cont'd

55

14 EP 0 128 006 B1

Compound R1 R2 n Physical No- constant 108-110°c (32) h /r-\ 2 m'p-

30 * 4 (33) -CH = N - CH = CH - 2 nD 1.5165 1 -, . ' 1.5142 10 (34) -CH = N - CH = N - 2 nD 144eC (35) H J*^ 2 m.p.

75 (36) H /r-T\ 2 Resinous product

(37) H -NH2 2 n^0-0 1.4778

20 (38) H _/C1 _/ ~\ 2 m. p. >300°C XC1 153°-155°C (39) H Cl 2 m.p. 25

n24'7 1.5930 30 (40) H rlk 2

COCKU II 3 o n24-2 35 (41) H a-* 2 1.5495

0 ' 5 (42) H -CH2COOCH3 2 n£8 1.4791 n20 ' 40 (43) H -CH(CH3)COOCH3 2 1.4694 208cC (44) H -CH2COOH 2 m.p." 2 nj7-5 1.5550 (45) H j-^ 45 -CH2-{ Y-Cl

Cont'd 50

55

15 EP 0 128 006 B1

Compound R R n Physical No. constant n*7 * 3 (46) H -CHCH3CN 2 1.4855

(47) H -C(CH3)2CN 2 n^7'3 1.4796

(48) H 1 n^5'0 1.4819 10 -CH2CN

(49) H -CH2CN 4 n^'1 1.4921

3 L593° (50) H J7~\ nQ5'2 75

20 Method (c) :

When the present compound is an acid amide compound represented by the formula (VIII),

25

n (VIII)

30

wherein R3, X and n represent the same meanings as above, provided that when X is an oxygen atom and Ft1 is a hydrogen atom, the following combinations of n and R3 are excluded : n = 1 and R3= methyl or phenyl; R = 2 and R3 = methyl, propyl, phenyl, chloromethyl, trichloromethyl, tert-butyl or trifluoromethyl; 35 n = 3 and R3 = methyl or trifluoromethyl; n = 4 and R3 = methyl, when X is an oxygen atom, R1 is benzyl and n is 1 , R3 is not methyl, and when X is an imino group, R1 is a hydrogen atom and n is 2, R3 is not a trichloromethyl group, it can be produced, for example, by reacting a compound represented by the formula (IX),

40

NHRJ (CH-) (IX) .2 n 45

wherein R1 and n represent the same meanings as above, with 1 .0 to 1 .1 equivalent of a compound represented by the formula (X),

50 M - C - R" (X) I! X

55 wherein R3 and X represent the same meanings as above, and M represents a halogen atom, a hydroxy, lower alkoxy, mercapto or lower alkylthio group, or a group represented by the formula

16 EP 0 128 006 B1

-0 - C - R3

5 (in which R3 and X represent the same meanings as above), at -78° to 200 °C for several minutes to 24 hours in a solvent in the presence or absence of 1.0 to 1.1 equivalent of an acid-binding agent, or by simply heating the both compounds at high temperatures and removing the formed hydrogen chloride, water, lower alcohol, hydrogen sulfide or lower mercaptan. As the above compound represented by the formula (X), there are given for example formic acid, ethyl 10 formate, acetic acid, acetyl chloride, propionic acid, propionyl chloride, 2-methylpropionic acid, 2-methyl- propionyl chloride, 2,2-dimethylpropionic acid, 2,2-dimethylpropionyl chloride, 3,3-dimethylbutanoic acid, 3,3-dimethylbutanoyl chloride, myristic acid, 2,2,3,3,3-pentafluoropropionic acid, 2,2,3,3,3-pen- tafluoropropionyi chloride, chloroacetyl chloride, trichloroacetyl chloride, chloroacetic acid, trichloroacetic acid, dichloroacetic acid, dichloroacetyl chloride, methoxyacetyl chloride, methoxyacetic acid, £-menthox- 15 yacetic acid, £-menthoxyacetyl chloride, cyanoacetic acid, cyanoacetyl chloride, methyl cyanoacetate, ethyl cyanoacetate, phenoxyacetic acid, phenoxyacetyl chloride, phenylthioacetic acid, phenylthioacetyl chloride, phenylacetic acid, phenylacetyl chloride, o-, m or p-chlorophenylacetic acid, o-, m- or p-chlorophenylacetyl chloride, a-chlorophenylacetic acid, a-chlorophenylacetyl chloride, crotonic acid, crotonyl chloride, 2- phenylpropionic acid, 2-phenylpropionyl chloride, o-, m- or p-tolylacetic acid, o-, m- or p-tolylacetyl chloride, 20 3-chloropropenoic acid, 3-chloropropenoyl chloride, propargylic acid, methyl propargylate, ethyl propar- gylate, 2-butynoic acid, ethyl 2-butynoate, 3-butynoic acid, 3-butynoyl chloride, methyl 3-butynoate, ethyl 3- butynoate, cyclohexanecarboxylic acid, cyclohexanecarbonyl chloride, cyclobutanecarboxylic acid, cyclobutanecarbonyl chloride, cyclopropanecarboxylic acid, cyclopropanecarbonyl chloride, 3-cyclohex- enecarboxylic acid, 3-cyclohexenecarbonyl chloride, benzoic acid, benzoyl chloride, o-, m- or p-chloroben- 25 zoic acid, o-, m- or p-chlorobenzoyl chloride, o-, m- or p-methylbenzoic acid, o-, m- or p-methylbenzoyl chloride, salicylic acid, o-, m- or p-methoxybenzoic acid, o-, m- or p-methoxybenzoyl chloride, 2,6- dimethylbenzoic acid, 2,6-dimethylbenzoyl chloride, 2,4-dichlorobenzoic acid, 2,4-dichlorobenzoyl chloride, o- or m-trifluoromethylbenzoyl chloride, o- or m-trifluoromethylbenzoicacid, p-fluorobenzoic acid, p- fluorobenzoyl chloride, 4-tert-butylthiobenzoic acid, O-ethyl 4-tert-butylthiobenzoate, ethyl 4-tert-butyl- 30 dithiobenzoate, 1-naphthoic acid, 1-naphthoyl chloride, 2- or 3-furoic acid, 2- or 3-furoyl chloride, 2,5- dimethyl-3-furoic acid, 2,5-dimethyl-3-furoyl chloride, 3-methyl-2-furoic acid, 3-methyl-2-furoyl chloride, isonicotinic acid, isonicotinyl chloride, N-methylpyrrole-2-carboxylic acid, N-methylpyrrole-2-carbonyl chlo- ride, 2-quinoxalinecarbonyl chloride, 2-quinoxalinecarboxylic acid, 2-thiophenecarboxylic acid, 2- thiophenecarbonyl chloride 2-benzimidazolecarboxylic acid, 3-methyl-5-isoxazolecarboxylic acid, 3- 35 methylisoxazolecarbonyl chloride, 2,4-dimethyl-4-oxazolinecarboxylic acid, 2,4-dimethyl-4-oxazolinecarbonyl chloride, 2-pyrazinecarboxylic acid, 2-pyrazinecarbonyl chloride, 2,4-dihydroxypyrimidine-5-carboxylic acid, 1 ,2,4-triazole-5-carboxylic acid, 1 ,4-benzdioxane-2-carboxylic acid, 1 ,4-benzdioxane-2-carbonyl chloride, 4- pyrazolecarboxylic acid, 5-imidazolecarboxylic acid, 2,3-dihydro-6-methyl-5-oxathiinecarboxylic acid, 2,3- dihydro-6-methyl-5-oxathiinecarbonyl chloride, succinic acid, maleic acid, phthalic acid, itaconic acid, 40 monomethyl succinate, monoethyl maleate, monoethyl phthalate, monoethyl itaconate, tetrachlorophthalic acid, dimethylmaleic acid, monoethyl tetrachlorophthalate, monoethyl 2,2-dimethylglutarate, glutaric acid, 2,2-dimethylglutaric acid, monoethyl glutarate, monoethyl 2,2-dimethylglutarate, 3,3-dimethylglutaric acid, citraconic acid, monoethyl 3,3-dimethylglutarate, monoethyl citraconate, tetrabromophthalic acid, monoethyl tetrabromophthalate, dithioacetic acid, trifluorodithioacetic acid, dithiobenzoic acid, O-ethyl thioacetate, 0- 45 methyl thiobenzoate, O-methyl p-methoxythiobenzoate, thioacetyl chloride, ethyl dithioacetate, methyl dithioisovalerate, methyl p-chlorodithiobenzoate, methyl p-hydroxydithiobenzoate, o-iodobenzoic acid, o- iodobenzoyl chloride, imidazolylacetic acid, triazolylacetic acid, 3,5-bis(trifluoromethyl)benzoic acid, 3,5-bis- (trifluoromethyl)benzoyl chloride, 5-chloropentanoyl chloride, diphenylacetyl chloride, 4-chloro-2-methyl- phenoxyacetic acid, benzoylformyl chloride, 1 ,4-benzdioxane-6-acetyl chloride, 3-chloropropionyl chloride, so butanoyl chloride, 3-methylbutanoyl chloride, bromoacetyl bromide, isobutoxyacetyl chloride, propenoyl chloride, 3-ethoxypropenoyl chloride, cinnamoyl chloride, 2-fluorocinnamoyl chloride, m-nitrobenzoyl chlo- ride, 2-phenylcyciopropanecarbonyl chloride, 1-methylcyclopropanecarbonyl chloride, 2,2,3,3-tetramethyl- cyclopropanecarbonyl chloride, m-bromobenzoyl chloride, m-cyanobenzoyl chloride, p-dimethylaminoben- zoyl chloride, m-fluorobenzoyl chloride, 2-chloro-4-nitrobenzoyl chloride, m-fluorobenzoic acid, 2-nitro-3- 55 phenoxybenzoyl chloride, 2,2-dimethyl-3-(2,2-dichloroethenyl)cyclopropanecarboxylic acid chloride, nicotinic acid, 3,5-dichlorobenzoyl chloride, nicotinyl chloride, pyrrole-2-carbonyl chloride, propyl 3-chloroformyl-3- butenoate, pyrrole-2-carboxylic acid, 3-methylbenzofuran-2-carboxylic acid chloride, chloroacetimidoyl chlo- ride, methyl 3-chloroformylpropanoate, trichloroacetimidic acid and the like.

17 EP 0 128 006 B1

Also, as an acid anhydride among the compounds represented by the formula (X), there are given for example anhydrides of the following compounds : Acetic acid, propionic acid, 2-methylpropionic acid, 2,2- dimethylpropionic acid, 3,3-dimethylbutanoic acid, myristic acid, 2,2,3,3-pentafluoropropionic acid, chloroacetic acid, dichloroacetic acid, trichloroacetic acid, methoxyacetic acid, i-menthoxyacetic acid, 5 cyanoacetic acid, phenoxyacetic acid, phenylthioacetic acid, phenylacetic acid, o-, m- or p- chlorophenylacetic acid, a-chlorophenylacetic acid, crotonic acid, 2-phenylpropionic acid, o-, m- or p- tolylacetic acid, 3-chloropropenoic acid, propargylic acid, 2-butynoic acid, 3-butynoic acid, cyclohexanecar- boxylic acid, cyclobutanecarboxylic acid, cyclopropanecarboxylic acid, 3-cyclohexenecarboxylic acid, ben- zoic acid, o-, m- or p-chlorobenzoic acid, o-, m- or p-methylbenzoic acid, salicylic acid, o-, m- or p- 10 methoxybenzoic acid, 2,6-dimethylbenzoic acid, 2,4-dichlorobenzoic acid, o- or m-trifluoromethylbenzoic acid, p-fluorobenzoic acid, 1-naphthoic acid, 2- or 3-furoic acid, 2,5-dimethyl-3-furoic acid, 3-methyl-2-furoyl chloride, isonicotinic acid, N-methylpyrrole-2-carboxylic acid, 2-quinoxalinecarboxylic acid, 2-thiophenecar- boxylic acid, 2-benzimidazolecarboxylic acid, 3-methyl-5-isoxazolecarboxylic acid, 2,4-dimethyl-4-ox- azolinecarboxylic acid, 2-pyrazinecarboxylic acid, 2,4-dihydroxypyrimidine-5-carboxylic acid, 1 ,2,4-triazole- 75 5-carboxyIic acid, 1 ,4-benzdioxane-2-carboxylic acid, 4-pyrazolecarboxylic acid, 5-imidazolecarboxylic acid, 2,3-dihydro-6-methyl-5-oxathiinecarboxylic acid, n-butyric acid, n-valeric acid, isovaleric acid, lauric acid, caproic acid, trifluoroacetic acid and the like.

Method (d) : 20 When the present compound is an acid amide compound represented by the formula (XI),

(CH ) / V 'XI' ' .2'n / NC - Z'COH

30 wherein R9 represents a hydrogen atom, a hydroxy, lower cycloalkyl, lower cycloalkenyl, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, arylcarbonyloxy or aryl group, a lower alkyl group which may be substituted with a halogen atom or a cyano, hydroxy, lower alkoxy, lower cycloalkyl, aryl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, or a lower alkoxy group 35 which may be substituted with an aryl group, Z' represents a cycloalkenylene, cycloalkylene, bicycloal- kylene or arylene group, a lower alkylene group which may be substituted with a hydroxy, lower alkoxy, aryl, lower alkylcarbonyloxy, methylene, alkylidene, mercapto, carbamoyloxy group which may be substi- tuted, or lower alkylcarbonylthio group, or a lower alkenylene group which may be substituted with a halogen atom or a carboxy or aryl group, and n represents the same meaning as above, 40 it can be produced, for example, by reacting a compound represented by the formula (XII),

(CH2)n/-NHR9

wherein R3 and n represent the same meanings as above, so with 1 .0 to 1 .1 equivalent of a compound represented by the formula (XIII),

O

55 c>V (xiii) Y o

18 EP 0 128 006 B1

wherein Z1 represents the same meaning as above, at -78° to 200° C for 1 to 24 hours with or without a solvent. As the compound represented by the formula (XIII), there are given for example the anhydrides of succinic acid, maleic acid, phthalic acid, itaconic acid, tetrachlorophthalic acid, dimethylmaleic acid, glutaric 5 acid, 2,2-dimethylglutaric acid, 3,3-dimethylglutaric acid, citraconic acid, tetrabromophthalic acid, 1,2- cyclohexanedicarboxylic acid, isopropylidenesuccinic acid, 3,4,5,6-tetrahydrophthalic acid, mellitic acid, 4- carboxyphthalic acid, dichloromaleic acid, phenylmaleic acid, 3-nitrophthalic acid, 1 ,2-pyridinedicarboxylic acid, 3,4-furandicarboxylic acid, 3,4-pyrazinedicarboxylic acid, naphthalic acid, 1 ,2-cyclobutanedicarboxylic acid, monochloromaleic acid, monobromomaleic acid, dibromomaleic acid, monofluoromaleic acid, 10 difluoromaleic acid, malic acid, thiomalic acid, methoxysuccinic acid, 2-methyl-2-phenylsuccinic acid, acetoxysuccinic acid, acetylthiosuccinic acid, tetrafluorophthalic acid, 5-norbornane-2,3-dicarboxylic acid, 1 ,2-dimethyl-1 ,2-cyclopropanedicarboxylic acid, camphanic acid, diphenic acid, diphenylcarbamoyloxysuc- cinic acid, cis, cis, cis, cis-1,2,3,4-cyclopentanetetracarboxylic acid and the like.

75 Method (e) :

When the present compound is an acid amide compound represented by the formula (XIV),

f \ Ri0 (CH-) V2 n

25 wherein R10 represents a lower cycloalkyl, lower cycloalkenyl, arylthio lower alkynyl, tetrahydrofurfuryl, piperidyl, arylcarbonyloxy or aryl group, a lower alkyl group which may be substituted with a halogen atom or a cyano, hydroxy, lower cycloalkyl, aryl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, or a lower alkenyl group which may be 30 substituted with a halogen atom or an aryl group, and R3 and n represent the same meanings as above, it can be produced by reacting a compound represented by the formula (XV),

35 (XV)

40 wherein R3, X and n represent the same meanings as above, with not less than the equivalent of a compound represented by the formula (XVI),

R10- L' (XVI)

45 wherein R10 represents the same meaning as above, and L' represents a halogen atom, an arylcarbonyloxy or lower alkylsulfonyloxy group, or a benzenesulfonyloxy group which may be substituted with a lower alkyl group, with or without a solvent at 0° to 150° C for 1 to 24 hours in the presence of not less than the equivalent of an acid-binding agent. 50 Method (f) :

When the present compound is represented by the foregoing formula (VIII) (provided that when X is an oxygen atom and R1 is a hydrogen atom, the following combinations of n and R3 are excluded : n = 1 and 55 R3= methyl or phenyl; n = 2 and R3 = methyl, propyl, phenyl, chloromethyl, trichloromethyl, tert-butyl or trifluoromethyl; n = 3 and R3 = methyl or trifluoromethyl; n = 4 and R3 = methyl, when X is an oxygen atom, R1 is benzyl and n is 1, R3 is not methyl, and when X is an imino group, R1 is a hydrogen atom and n is 2, R3 is not a trichloromethyl group), it can also be produced, for example,

19 EP 0 128 006 B1

by reacting a compound represented by the formula (XVII),

H - N , (XVII) cir

wherein R1, R3 and X represent the same meanings as above, w with not less than the equivalent of a compound represented by the foregoing formula (VII) with or without a solvent at 0° to 150° C for 1 to 24 hours in the presence of not less than the equivalent of an acid-binding agent. As the compound represented by the formula (XVII), there are given for example formamide, pentan amide, butan amide, N-ethylacetamide, acetamide, chloroacetamide, dichloroacetamide, trichloroacetamide, 75 N-tert-butylacetamide, malonamide, IM-methylchloroacetamide, cyanoacetamide, N-(2-hydroxyethyl)- acetamide, methacrylamide, lactamide, 2,2-dimethylpropan amide, N-methylformamide, trifluoroacetamide, N-ethylformamide, octadecan amide, N-(hydroxymethyl)acrylamide, thioacetamide, propan amide, N-(2- chloroethyl)acetamide, N-methylacetamide, 2-hydroxybenzanilide, acetanilide, 2'-hydroxyacetamide, nicotinamide, formanilide, thioisonicotinamide, oj-thiocaprolactam, benzanilide, 5-chloro-2-hydroxyben- 20 zanilide, 3'-nitroacetanilide, 4'-chloroacetanilide, 3'-chloroacetanilide, 4-hydroxybenzamide, 3,5-dinitroben- zamide, 3-nitrobenzamide, benzhydroxamic acid, 2',5'-dichloroacetanilide, 2-cyanobenzamide, ac- etylacetanilide, 2'-methylacetanilide, 2,6-dichlorobenzamide, 2'-chloroacetylacetanilide, 21- methylacetylacetanilide, phenylacetamide, pyrazine-2-carboxamide, N-methyl-2-methylbenzamide, N- methylbenzamide, 3,4,5-trimethoxybenzamide, 3-chloroacetanilide, 4'-chloroacetylacetanilide, 4-nitroben- 25 zamide, 2-cyanoacetanilide, 2-chlorobenzamide, 2-nitrobenzamide, 3'-hydroxyacetanilide, 3'- methylacetanilide, 3-chlorobenzamide, 4'-hydroxyacetanilide, 2'-hydroxyacetanilide, 2-pyrrolidone, 1 ,2-ben- zisothiazol -3(2H)-one and the like.

Method (g) : 30 When the present compound is an acid amide compound represented by the formula (XVIII),

35 I (xviii) . v-Nr ,

40 wherein R1, R3 and n represent the same meanings as above, it can be produced, for example, by reacting a compound represented by the formula (XIX),

f \ X I Vur _ (xix) ICH

20 EP 0 128 006 B1

isophorone, cyclohexanone, etc., esters such as ethyl formate, ethyl acetate, butyl acetate, diethyl carbonate, etc., nitro compounds such as nitroethane, nitrobenzene, etc., nitriles such as acetonitrile, isobutyronitrile, etc., tertiary amines such as pyridine, triethylamine, N,N-diethylaniline, tributylamine, N- methylmorpholine, etc., acid amides such as formamide, N,N-dimethylformamide, acetamide, etc., sulfur 5 compounds such as dimethyl sulfoxide, sulfolane, etc., and mixtures thereof. Also, the acid-binding agent includes for example organic bases such as pyridine, triethylamine, N,N-diethylaniline, etc., and inorganic bases such as sodium carbonate, potassium carbonate, sodium hydroxide, etc. After completion of the reaction, the reaction solution is after-treated as usual, and if necessary, the product obtained is purified by chromatography, distillation, recrystallization and the like. w Next, examples of production of the present compound by the methods (c) to (g) will be shown.

Production example 4

To a mixture of 2-cycloheptenylamine (1.11 g, 10 mmoles), triethylamine (1.01 g, 10 mmoles) and 75 chloroform (10 ml), propionyl chloride (0.93 g, 10 mmoles) was added dropwise at 0° to 5° C. After stirring at 20 °C for 3 hours, the reaction mixture was poured into a 1N hydrochloric acid, and the separated organic layer was washed with a saturated aqueous sodium chloride solution and concentrated to obtain 1.50 g of N-(2-cycloheptenyl)propionamide [Compound (51)]. m.p. 84° C 20 Production example 5

To a chloroform (50 ml) solution of succinic anhydride (1.00 g, 10 mmoles), 2-cycloheptenylamine ° (1.11g, 10 mmoles) was added dropwise at 0° to 5°C. After stirring at 61 C for 5 hours, the reaction 25 mixture was cooled to obtain a crystal. The crystal was recrystallized from an ethyl acetate/hexane mixture to obtain 1 .67 g of N-(2-cycloheptenyl)-1 ,4-butanedicarboxylic acid monoamide [Compound (52)]. m.p. 132° -133° C

Production example 6 30 To a dichloromethane solution (13 ml) containing salicylic acid (1.38 g, 10 mmoles), dicyclohexylcar- bodiimide (2.06 g, 10 mmoles) was slowly added at 0° C. After this mixture was stirred for 15 minutes, and 2-cyclohexenylamine (0.97 g, 10 mmoles) was added dropwise. The mixture was then heated to room temperature and stirred for 5 hours. 35 The formed crystal was filtered off, the floating solid was removed by filtration and 13 ml of cold water was added to the filtrate. The organic layer was separated and washed with 3M hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution in this order. After drying the organic layer over magnesium sulfate, the solvent was removed and the residual oil was purified by column chromatography on silica gel [ethyl acetate : hexane = 3:1 (v/v)] to obtain 1 .78 g 40 of N-(2-cyclohexenyl)salicylic acid amide [Compound (53)].

n£2'4 1-5781

45

Production example 7

To a suspension (10 ml) of sodium hydride (0.24 g, 10 mmoles) in dimethylformamide was added 50 dropwise at 0°C a dimethylformamide solution (1 ml) of N-methylbenzamide (1.35 g, 10 mmoles). After completion of the addition, the temperature was raised to room temperature, and after stirring for 15 minutes, 3-bromocycloheptene (1.75 g, 10 mmoles) was added dropwise. The resulting mixture was stirred at room temperature for 24 hours, poured into water (20 ml) and extracted with ether. The oily product obtained by concentration was purified by chromatography on silica gel to obtain 0.92 g of N-methyl-N-(2- 55 cycloheptenyl)benzamide [Compound (54)].

21 EP 0 128 006 B1

n^6'1 1.5467

Production example 8

To a suspension (10 ml) of sodium hydride (0.24 g, 10 mmoles) in DMF was added N-(2-cyclohep- tenyl)acetamide (1.53 g, 10 mmoles) in DMF (1 ml) at 0°C. After completion of the addition, the temperature w of the mixture was raised to room temperature, and after stirring for 15 minutes, methyl iodide (2.84 g, 20 mmoles) was added dropwise. The resulting mixture was stirred at room temperature for 24 hours, poured into water (20 ml) and extracted with ether. The oily product obtained by concentration was purified by chromatography on silica gel to obtain 0.84 g of N-methyl-N-(2-cycloheptenyl)acetamide [Compound (55)].

15 24 5 n^'° 1.4968

20 Production example 9

A mixture of N-(2-cyclohexenyI)-4-tert-butylbenzamide (3.78 g, 14.7 mmoles), phosphorus pentasulfide (1.65 g) and pyridine (17.6 ml) was heated under reflux for 3 hours. Thereafter, the reaction mixture was cooled, poured into water and extracted with ether. The organic layer was dried over anhydrous magnesium 25 sulfate and concentrated. The oily product obtained was purified by column chromatography on silica gel to obtain 0.71 g of the objective compound [Compound (205)]. ° m.p. 88-91 C Some of the present compounds which can be produced by these methods are shown in Table 2.

30

35

40

45

50

55

22 EP 0 128 006 B1

Table 2

Present compounds represented by the formula,

1

n w

r1 R3 Compound n x physical constant

(51) H 3 75 ~CH2CH3 ° m-P- 84CC

(52) H -CH2CH2COOH 3 0 m.p. 132-133'C

<53> H -/3 2 o n^2-4 1.5781 20 OH

<54> CH3 -O 3 ° "D6"1 l-5*61 25 (55) CH3 -CH3 3 0 n£4-5 1.4968 (56) H -CC1=CC1COOH 3 O m.p. 139-140° C (dec. )

30 (57) H ~CC13 3 0 "".p. 104-105°C

(58) H "CC13 3 ~NH m.p. 85-87°C

35 (59) H -CC1=CC1CNH^J) 3 0 m.p. 63-64°C 0

(60) H -CH2C1 3 0 m.p. 92*C

40 '61J H -CHj-^Q 3 0 m.p. 120'C

(62) H _Ch2o-/J\ 3 0 m.p. 92°C 45 wc"3 (63) H -\_J) 3 0 m.p. 113-114°C

50 CH3

55

23 EP 0 128 006 B1

Compound Rl r3 n x physical constant

<64> H -Q 3 0 m.p. 121"C

<65> H -^y 10 3 0 m.p. 116°C

<«> H 75 -kQ 3 0 m.p. 94eC

(") H -(_j 3 0 m.p. 161°C

20 <68> H -CH = CH2 3 0 m.p. 72-74°C

<69) H -CH2OCH3 3 0 m.p. 46-47°C

25 (?°) H -^y ■ 3 0 m.p. 147-148°C

<71' H ^X^ 3 17°6c 30 ° m'P'

(72> H -/jrNO2 3 0 m.p. 154-156*C

35 Cl

<73) H -Q- -3 0 m.p. 89-91°C

40 OCH,

(7'1) H -CH2CH2COOCH3 3 0 m.p. 65-67°C

45 ~i] <75> H 3 0 m.p. 120-121° C COOH

<76) H -CH = CHCOOH 114-115° 50 3 0 m.p. C

55

24 EP 0 128 006 B1

Compound Dl _3 n X Physical constant No. K R

{77) H ~{\ 3 0 m.p. 97-98°C

(78) H J^ J^J 3 0 n^3'9 1.5910 10

(79) H H 3 0 n^2"5 1.5050 pu v3 75 (80) H /[[ 3 0 m.p. 9l*C

(81) H -CHCl-f) 3 0 m.p. 120-1218C

20 NO2 i32"134'0 (82) H ~\_J 3 ° m-p*

25 ' 5 (83) H -C(=CH2)CH2- 3 0 n^5 1.4991 COO(CH2)2CH3

30 (84) H \—/\l 3 0 m.p. 117°C

ch'3 ch3

35 (85) H ~f_J 3 ° m-P- H7-118*C

(86) H "\3"CH3 3 ° m'P' 142°C 40

(87) H -/_\-OCH3 3 0 m.p. 145-147°C

45 -II \ (88) H Ci)Hg(t) 3 O m.p. 145-147°C

50

55

25 EP 0 128 006 B1

Compound ,R1 R3 n X Physical constant

(89) H -£\ 3 0 m.p. 137-138°C

<90> H -^J 3 0 174°C 70 m.p. NO-

(91> H -CH2Br 3 0 m.p. 173-174*C 75 (92) H -CH2CH2CH3 3 0 m.p. 76°C

(33) H -{h} 3 0 m.p. 166-169°C 20 (94) H -C(CH3)3 3 0 m.p. 119-120eC

(95) H -CH2CH2C1 3 0 m.p. 76-77eC 25 (96) H -CH

(97) H -/^] 3 0 m.p. 150°C

30 (98) H -CH2C(CH3)3 3 0 m.p. 132-133CC 5 (99) H -CH2Oiso-Bu 3 O n^4 • 1.4805

35 (100) H -CH2CH{CH3)2 3 O m.p. 117°C

H3CwCH3 dOD H ■ -

(102) H ^ ) 3 O 156-158°C 45 m.p.

(103) H -{} 3 0 m.p. 181-182'c

50

55

26 EP 0 128 006 B1

Compound Physical constant No. R

(104) m.p. 133-135°C CN

(105) -a m.p. 103-105°C 70

(106) -CH = CHOC2H5 0 m.p. 110-112°C

(107) -CH. 0 _23.2 , rn.n CH2CN D 1.5040 75 24.2 (108) CH2COOCH3 -CH. O 1.4817

(109) n"*1 1.5770 20 OH CH3 CH3

(110) -CH.O n*1"0 1.4950 25

CH-

(111) -CF = CH ■o m.p. 1138C 30

(112) -CH. m.p. 143'C

35 (113) -CH^S- m.p. 92 C

40 (114) -o m.p. 176 C

(115)

(116) 1" m.p. 93 C O 50

55

27 EP 0 128 006 B1

Compound Rl 3 n X Physical constant No. R 7 (117) -CH2CH = CH2 -CH3 3 0 n*3 * 1.5021

-A (118) -CH3 3 0 n^3-5 1.5076

10 (119) -CH2C = CH -CH3 3 0 n^8"5 1.5131

(120) -<^J) -CH3 3 0 n£°-7 1.5162

75

(121) ~CH2-£j -CH3 3 0 n^5-3 1.5329 / F 20 3 (122) -CH2CH2OCH2CH3 -CH3 3 0 nP " 1.4850

(123) H -CH^ 3 0 J.Org.Chem. 46, 4727 (1981)

25 (124) H -CH2O-^ J-Cl 3 0 m.p. 118*C

CH3

30 (125) ~\/y -CH2C1 3 O n^4-8 1.5373

(126) H -CH2CN 3 0 m.p. 131°C 35 (127) -CH(CH3)2 -CH2C1 3 O n^3*3 1.5044

P 40 ^ (128) -T J -CH^ 3 O ra.p. 147°C

45

(129) H "CH^C 3 ° m-p* 153°c

50

55

28 EP 0 128 006 B1

Compound V Physical constant No.

(130) -CH2CH2OCH2CH3 -CH2C1 n^6-6 1.5000

(131) m.p. 123 C 10 CH,

(132) -CHC1. n^6*1 1.5467 75

(133) -(CH2)4C1 O m.p. 71 C

(134) •(CH2)5C1 -CH. O n^2'5 1.4966 20 (135) -CH2CH2CH2- O n£4'3 1.5175

(136) -CHCH^COOCH. -CH OCH O n^3'7 1.4886 25

(137) m.p. 126 C CF. 30 (138) H -CH2CH3 m.p. 80-82 C

(139) H -CH_CH2COOH m.p. 143-144 C

35 (140) H -CH = CHCOOH m.p. 113-114 C CIU

(141) m.p. 91-93 C 40 CH-

(142) -CH. m.p. 108-111 C 45

(143) O m.p. 128-130 C

Cl 50

55

29 EP 0 128 006 B1

Compound Rl R3 n X Physical constant

\=J (144) H 2 0 m.p. 113-114CC Cl

10 (145) H ~W"C1 2 ° m#P' 162-164*C

(146) H -/) 2 0 m.p. 118-120*C 75 CH

(147) H -Q 2 0 m.p. 90-92°C 20 CH3

(148) H "C3~CH3 2 ° m-P' 133-135°c 25

(149) H -Q 2 0 n25"3 1.5568

30 0CH3

-J[\ (150) H 2 0 m.p. 1O1-1O3'C 35 OCH3

(151) H -£j-OCH3 2 0 m.p. 120-122°C

40

(152) H -(j 2 0 m.p. 160-162°C

CH3 45

-/ (153) H y-Cl 2 0 m.p. 143-145°C

50 Cl

55

30 EP 0 128 006 B1

Compound Dl D3 n X Physical constant No. R R ' * (154) -CH2CH3 -CH3 2 0 n^° 1.4840

(155) H i) 2 0 m.p. 86-87*C 10

(156) H -/^ 2 0 m.p. 116-118°C

15 (157) H -fj 2 ° m'P- 122-123°C

XF3

CA 20 H5-116

(159) H -CH(CH3>2 2 0 m.p. 107-108°C 25 (160) H -(CH2)12CH3 2 0 m.p. 82-83eC

(161) H -\BJ 2 0 m.p. 165-166°C 30 (162) H -CH2C(CH3)3 2 0 m.p. 118-121°C

(163) H -\\ 2 0 m.p. 107-108'c 35

(164) H -

40 (165) H -CH = CHCH3 2 0 m.p. 86-89°C

(166) H -CH2C(=CH2)COOH 2 0 m.p. 140-141°C

45 \ J[ 2 0 m.p. 116-119° C (167) H XJ CF3

50 (168) H -CHCl2 2 O m.p. 128-129°C

55

31 EP 0 128 006 B1

Compound hysical constant No. CH. (169) Xx m.p. 94-95 C

(170) ■O m.p. 115-120 C W

(171) -CH2CN -CH2C1 n^7-3 1.4855

O nj7-6 1.5650 75 (172) -CH2-f_J-Cl -CH2C1

(173) -CH2COOCH3 -CH..C1 rip7'5 1.5070

20 (174) -CH. m.p. 116-117 C

(175) •CH. m.p. 157-158 C 25

(176) -cH2i rCH3 m.p. 134-135 C

30 m.p. 90-91 C (177) "CH2i CH-

35 -CH. 2 O m.p. 141-142 C (178) CH-

40 -CH. m.p. 150-151 C (179) Cl

45 m.p. 136-138 C (180) COOH nP'5 (181) -CH2OCH3 1.4866 50

55

32 EP 0 128 006 B1

" r— — i "j j "Compound 1 3 n X Physical constant No.

(182) H -CH 0-f ) 2 0 m.p. 62-63'c

10 (183) H -CH2O-LLJ 2 0 n20'5 1.4920

H3C CH3

75 (184) H -CHCl-^ J 2 0 m.p. 109-112°C

-ch,-/ y 20 (185) H ^W 2 0 m.p. 110-lll°C Cl

J-Am.Chem.Soc. . , H on2 0 , 94, (186) CH3 ?892 (19?2) — 25 Can. M . H„ _„„ r1 2on O J.Chem.55,— (187) CH2C1 7Q0 (lg?7)

. H -rirH i 2■? 0n J-Am.Chem.Soc.89, (188) C(CH3)3 6303 (1967) 30 -/~\ uH 2 0 J-Am-Chem.Soc.8£, UBy) >t=/ 4312 (1958)

(190) H -CC1 2 0 J-Am.Chem.Soc.98, 11SU| H UL13 2901 (1976) 35 (191) H -CH = CHC1 2 0 m.p. 87-88CC

(192) H H 2 0 rip0'0 1.5050

(193) H -CH-CN 2 0 m.p. 110-115°C 40 1

(194) H -CH?S-^ J 2 0 m.p. 67-68°C

45 (195) H f*12*"^!!55] 2 ° m"P" 153~156°c

(196) H ~CC13 2 NH Ger.Offen.2,601,137 50 (197) H -CF2CF3 2 0 m.p. 72-73°C

55

33 EP 0 128 006 B1

Compound 1 3 n X Physical constant No. R R

(198) H ■/ Vf 2 0 m.p. 120-122°C

-/ \ (199) H 2 0 m.p. 170-172*C 10

-/ \ (200) H 2 0 m.p. 85-86°C IT

15

(201) H ""^-N^S^ 2 ° m-p- 7°-75°C

20 (202) H ~CH2\ / C1 2 ° m*p* 138~139 c

(203) H -CH3 2 S m.p. 57-59°C

25 129-130°C (204) H -\ y 2 0 m.p.

(205) H O0^^ 2 S m.p. 88-91°C 30 CH, CH (206) H 1 1 2 0 Resinous product I J COOH

35 (207) H -CC1 = CC1COOH 2 0 m.p. 106-109°C

(208) -CH(CH3)COOCH3 -CH2C1 2 0 n24"0 1.5090

40 (209) H -CH?l|*N 2 0 m.p. 108-110°C

(210) H -CH-N^ ^ 2 0 m.p. 152°C 2Wr/

45 (211) H -/3 2 0 m.p. 110-112

(213) ° nD4'8 50 y-^" 2 1-6314

55 Method (h) :

When the present compound is an acid imide compound represented by the formula (XX),

34 EP 0 128 006 B1

n /VZ

wherein X, Y, Z and n represent the same meanings as above, provided that a case wherein when n is 2 or w 3 and X and Y are an oxygen atom, Z is an o-phenylene group, is excluded, it can be produced by reacting cycloalkenylamine represented by the formula (XXI),

75 {XXI> (CH2)n/NH2

20 wherein n represents the same meaning as above, with 0.9 to 1 .0 equivalent of a compound represented by the formula (XXII),

25 X HO Jk Z (XXII) HO -tT-/

30 ^

wherein X, Y and Z represent the same meanings as above, or its anhydride, i.e. a compound represented by the formula (XXIII)

35 X li O'^^Z (XXIII)

Y 40 wherein X, Y and z represent the same meanings as above, with or without a solvent at 80° to 180° C, preferably 130° to 160° C for 1 to 30 hours in the presence or absence of a catalyst. As the compound represented by the formula (XXII), there are given for example succinic acid, 1,2- 45 cyclohexanedicarboxylic acid, maleic acid, citraconic acid, isopropylidenesuccinic acid, 3,4,5,6- tetrahydrophthalic acid, mellitic acid, 4-carboxyphthalic acid, dichloromaleic acid, phenylmaleic acid, tetrachlorophthalic acid, tetrabromophthalic acid, 3-nitrophthalic acid, 1 ,2-pyridinedicarboxylic acid, 3,4- furandicarboxylic acid, glutaric acid, 2,2-dimethylglutaric acid, 3,4-pyrazinedicarboxylic acid, 3,3-dimethyl- glutaric acid, dimethylmaleic acid, naphthalic acid, 1 ,2-cyclobutanedicarboxylic acid, monochloromaleic so acid, monobromomaleic acid, dibromomaleic acid, monofluoromaleic acid, difluoromaleic acid, malic acid, thiomalic acid, methoxysuccinic acid, 2-methyl-2-phenylsuccinic acid, acetoxysuccinic acid, acetylthiosuc- cinic acid, tetrafluorophthalic acid, 5-norbomane-2,3-dicarboxylic acid, 1 ,2-dimethyl-1 ,2-cyclopropanedicar- boxylic acid, itaconic acid, camphanic acid, diphenic acid, diphenylcarbamoyloxysuccinic acid, phenylcar- bamoyloxysuccinic acid, cis, cis, cis, cis-1,2,3,4-cyclopentanetetracarboxylic acid, bicyclo[2,2,2]octa-5-ene- 55 2,3-dicarboxylic acid and the like. As the compound represented by the formula (XXIII), there are given the anhydrides of the compounds represented by the foregoing formula (XXII).

Method (i) :

35 EP 0 128 006 B1

When the present compound is an acid imide compound represented by the foregoing formula (XX) (provided that a case wherein when n is 1 , 2 or 3 and X and Y are an oxygen atom, Z is an o-phenylene group, is excluded), it can be produced by reacting a compound represented by the foregoing formula (VII) with 1 .0 to 1 .1 equivalent of a compound represented by the formula (XXIV), 5 X ii HN Z (XXIV)

wherein X, Y and Z represent the same meanings as above, with or without a solvent at 0° to 200° C, preferably 20° to 160° C for 1 to 24 hours in the presence of 1.0 75 to 1 .1 equivalent of an acid-binding agent. As the compound represented by the formula (XXIV), there are given for example acid imides corresponding to the compounds represented by the foregoing formula (XXIII) and the compounds described below : 5,5-Dimethyl-2-thioxo-4-oxazolidinone 20 5,5-Dimethyl-4-thioxo-2-oxazolidinone 5,5-Dimethyl-2,4-thiazolidinedione 2-Thioxo-4-imidazolidinone 2,4-lmidazolidinedione 5,5-Dimethyl-2,4-oxazolidinedione 25 5,5-DimethyI-2-thioxo-4-imidazolidinone 5,5-Dimethyl-2,4-imidazolidinedione 5,5-Dimethyl-2-thioxo-4-thiazolidinone 5-lmino-2-pyrrolidinone

30 Method (j) :

When the present compound is an acid imide compound represented by the formula (XXV),

r\x

40 wherein X, Z and n represent the same meanings as above, it can be produced by reacting an acid imide compound represented by the formula (XXVI),

45

(XXVI) (C«2}n

50

wherein X, Z and n represent the same meanings as above, with 1 or 2 equivalents of phosphorus pentasulfide at 25° C to 150° C for 1 to 24 hours in the presence or absence of a solvent. 55 The acid imide compound represented by the formula (XXVI) is obtained by the foregoing method. The solvent used in the methods (h) to (j) includes for example aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, etc., aromatic hydrocarbons such as benzene, toluene, xylene, etc., halogenated hydrocarbons such as chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dich-

36 EP 0 128 006 B1

lorobenzene, etc., ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, diethylene glycol dimethyl ether, etc., fatty acids such as formic acid, acetic acid, oleic acid, etc., alcohols such as methanol, ethanol, isopropanol, tert-butanol, octanol, cyclohexanol, methyl cellosolve, diethylene glycol, glycerin, etc., nitro compounds such as nitroethane, nitrobenzene, etc., nitriles such as acetonitrile, isobutyronitrile, etc., 5 tertiary amines such as pyridine, triethylamine N,N-diethylaniline, tributylamine, N-methylmorpholine, etc., sulfur compounds such as dimethyl sulfoxide, sulfolane, etc., water and mixtures thereof. Also, the acid-binding agent includes for example organic bases such as pyridine, triethylamine, N,N- diethylaniline, etc. and inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogen- carbonate, potassium hydroxide, sodium hydroxide, sodium hydride, etc. w After completion of the reaction, the reaction solution is after-treated as usual, for example an organic solvent is added to the solution which is then washed with an alkali and water to obtain the objective compound. If necessary, the compound obtained is purified by chromatography, distillation, recrystallization and the like. Next, examples of production of the present compound by the methods (h) to (j) will be shown. 75 Production example 10

A mixture of 2-cycloheptenylamine (1.01 g), succinic anhydride (1.0 g) and acetic acid (10 ml) was heated under reflux for 24 hours. After cooling, ether (20 ml) was added to the reaction mixture which was 20 then washed with a saturated aqueous sodium hydrogencarbonate solution, water and a saturated aqueous sodium chloride solution in this order. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The oily product thus obtained was purified by column chromatography on silica gel to obtain 1.07 g of N-(2-cycloheptenyl)succinimide [Compound (214)].

n^4-3 1.4872

30 Production example 1 1

A mixture of N-2-cycloheptenyl-3,4,5,6-tetrahydrophthalimide (3.75 g), phosphorus pentasulfide (3,40 g) and toluene (10 ml) was heated under reflux for 5 hours. The reaction mixture was cooled, poured into water and extracted with ether. The organic layer was dried over anhydrous magnesium sulfate and 35 concentrated. The oil obtained was purified by column chromatography on silica gel to obtain 1.51 g of the objective compound [Compound (215)].

40 n^2'5 1-6604

Production example 12 45 A mixture of 2-cycloheptenylamine (1.11 g), 1 ,2-dimethyl-1 ,2-cyclopropanedicarboxylic acid (1.58 g) and toluene (30 ml) was heated, and formed water was removed azeotropically. Thereafter, the mixture was concentrated, and the oily product obtained was purified by chromatography on silica gel to obtain 1.26 g of N-(2-cycloheptenyl)-1 ,2-dimethyl-1 ,2-cyclopropanedicarboxyimide [Compound (216)]. 50 m.p. 57-59° C

Production example 13

A mixture of 2-cycloheptenylamine (1.01 g), dichloromaleic anhydride (1.67 g) and acetic acid (10 ml) 55 was heated under reflux for 3 hours. After cooling, ether (20 ml) was added to the reaction mixture which was then washed with a saturated aqueous sodium hydrogencarbonate solution, water and a saturated aqueous sodium chloride solution in this order. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The deposited crystal was purified by recrystallization from hexane to obtain 1.67

37 EP 0 128 006 B1

g of N-(2-cycloheptenyl)dichloromaleinimide [Compound (217)]. ° m.p. 90-91 C

Production example 14 5 3-Bromocycloheptene (1.75 g) was added dropwise at room temperature to a DMF suspension (10 ml) of sodium succinimide prepared from succinimide (0.99 g) and 60% sodium hydride (0.40 g). This mixture was stirred at room temperature for 24 hours, poured into water (10 ml) and extracted with ether. The oily product obtained by concentration was purified by chromatography on silica gel to obtain 0.09 g of N-(2- io cycloheptenyl)succinimide [Compound (214)].

n 1.4875

75 Some of the present compounds similarly obtained are shown collectively in Table 3.

20

25

30

35

40

45

50

55

38 EP 0 128 006 B1

Table 3

Present compounds represented by the formula,

10 Compound X Y Z n Physical constant No. n24 ' 3 (214) 0 0 -CH2CH2- 3 1.4872 15 (215) S S T^l 3 nD2'5 1"6004

57-59°C 20 (216) 0 0 P> 3 m.p. CH3

(217) O 0 -CC1 = CC1- 3 m.p. 90-91°C 25 (218) 0 O -S - C(CH3)2- 3 m.p. 86-88°C

(219) 0 0 -CBr = CBr- 3 m.p. 134-135°C

30 (220) 0 0 -CC1 = CH- 3 m.p. 100°C

(221) 0 0 -CBr = CH- 3 m.p. 114-116°C

(222) 0 0 -CH = CH- 3 n25*9 1.5732 35 * (223) 0 0 -C(CH3) = CH- 3 nD 1.5748 n22"6 (224) O 0 -C(=CH2)CH2- 3 1.5862

40 3 0 -Ct-C^ 3)CH_- 3 n*9 " 1.5892 (225) O ^ CH^

(226) 0 0 ^Q 3 m.p. 175-177°C 45 1 NO2

50

55

39 EP 0 128 006 B1

Compound X Y z n Physical constant No.

(227) 0 0 ¥*| 3 m.p. 156°C

(228) 0 O T"^) 3 m"p- 81-83°C

10 -CH = CH2-

(229) 0 0 j^JJ 3 m.p. 84-86°C

75 (230) 0 0 -CH2- CH(OH)- 3 m.p. 121-123°C

(231) 0 0 -CH2CH(SH)- 3 m.p. 64-67°C ° (232) 0 0 -CH2CH(OCH3)- 3 n33 " 1.5621 20 0 (233) 0 0 -CH2CH(O(i:CH3)- 3 m.p. 86-88°C

0 25 (234) 0 0 -CH2CH(SCCH3)- 3 m.p. 93-9S°C

(235) 0 0 3 n21'7 1.5741

30 (236) 0 0 XO 3 nD5'3 1-5329

-C(CH3)CH2-

35 (237) 0 0 ^> 3 n2D2-5 1.5505

(238) S 0 -NHCH - 3 m.p. 148°C

40 (239) 0 0 3Cj 3 m'P" 102°C

" 4 (240) 0 0 -C(CH3) = C(CH3»- 3 n^7 1.5689 45 t \=^ 2J 2 (241) 0 0 ^ 3 m>p_ 53=c

(242) S O -S - CH2- 3 n^2"0 1.5535 50

55

40 EP 0 128 006 B1

Compound X Y Z n Physical constant No. . p 173"174<>C (243) 0 0 *""££ 3 m'P"

F

10 "y*1^ Eur.J.Med.Chem.13, ,„,,, n _ 3, — (244) 0 0 j^Jj 81 {1978)

n28 ' 2 (245) 0 0 -CH2CH2- 2 1.5192 75 ' (246) 0 0 -CH = CH- 2 n23 1.5211

(247) 0 0 -CC1 = CC1- 2 m.p. 89"C-

20 ^T*15^ „ Chem.S. Ind. 414, (248) 0 O J^Jj 2 (1958)

(249) 0 0 ~T"D 2 "•p" 46-48°C 25 (250) 0 0 ^iT JI l m"P" 41~44°C

20 ' 4 (251) 0 0 -C(CH3) = CH- 4 np 1.5227 30 20 ' 4 (252) O O -C(=CH2)CH2- 4 nD 1.5331

(253) O S "T^l 2 m'P' 45~48°C 35 '* O O -C(=Cy 3\CH,- 2 n" 1.5361 (254) ^ CH3/

40 (255) O 0 ^C3 2 m'P* 100~101°C

NO2

76°C 45 (256) O O Xj 2 m'P'

(257) O O XT^3 2 m*P" 67°C 50

55

41 EP 0 128 006 B1

Compound X Y Z n Physical constant No. -C = CH - * (258) O O l^^ 2 m.p. 140cC

10 (259) 0 0 -CC1 = CC1- 4 m.p. 63~64CC

(260) 0 O \ S 2 n25"0 1.5079

CH, CH3 15 (261) 0 0 -OC(CH3)2- 2 m.p. 69-71°C

(262) 0 S -NHCH2- 2 m.p. 106-108°C

20 (263) 0 0 -CH = CC1- 2 m.p. 78°C

(264) O 0 -CH = CBr- 2 m.p. 90-91°C

(265) 0 0 . -C(CH3) = CH- 2 m.p. 65-66°C 25 (266) 0 O -CC1 = CC1- 1 m.p. 52°C

(267) 0 0 -NHCH2~ 2 m.p. 91°C

(268) 0 0 = n25 - 2 30 -C(CH3) C(CH3)- 2 1.5178 5 (269) O 0 -CH2CH(SCOOCH3)- 2 n29 ' 1.5344

(270) O 0 2 n29"5 1.5220 35

(271) O O ~X^jX 2 m-P" 97°C

(272) O O 2 108-110°C 40 -CH(OH)CH2- m.p.

(273) O O -CH(OCOCH3)CH - 2 m.p. 96°C

(274) 0 O -CH(OCH3)CH2- 2 n^0"7 1.5110 45 (275) O O -CH(SH)CH2- 2 "q9*7 1.5490

(276) O O -CH(OCNH-^3)CH2~ 2 m"P" 165-168°c O 50 (277) O O -CBr = CBr- 2 m.p. 81°C

55 Method (k) :

When the present compound is an imine compound represented by the formula (XXVII),

42 EP 0 128 006 B1

,r' VN = C (XXVII) (C"2'n/| NR5«-

wherein R4, R5 and n represent the same meanings as above, provided that the following cases are excluded : when n is 1, R4 is a butyl group and Rs is a pentyl group, or R4 and R5, taken together, form a 10 2,4,4-trimethyl-1-pentenylene group; and when n is 2, R4 and R5, taken together, form a pentenyiene group, it can be produced by reacting cycloalkenylamine represented by the foregoing formula (XXI) with 0.95 to 1.0 equivalent of a carbonyl compound represented by the formula (XXVIII),

75 R4 O = C^ (XXVIII) 5 R

20 wherein R4 and R5 represent the same meanings as above, at 0° to 150° C for 1 to 24 hours with or without a solvent. As the carbonyl compound represented by the above formula (XXVIII), there are given for example formaldehyde, acetaldehyde, propionaldehyde, glyoxylic acid, methoxyacetaldehyde, butylaldehyde, isobutylaldehyde, n-valeraldehyde, isovaleraldehyde, 2-methylbutylaldehyde, hexanal, heptanal, octanal, 25 decanal, ,8-phenylpropionaldehyde, dodecanal, 5-norbomane-2-carboaldehyde, cyclohexanecarboaldehyde, cyclooctanecarboaldehyde, 2-ethylbutanal, phenylacetaldehyde, chloroacetaldehyde, chloral, cinnamal- dehyde, a-methylcinnamaldehyde, a-bromocinnamaldehyde, a-chlorocinnamaldehyde, acrolein, acrolein dimer, metacrolein, crotonaldehyde, trans-2-hexenylaldehyde, 2-ethyl-2-butenal, 2-ethylhexanal, citral, citronellal, phenyipropargylaldehyde, DL-glyceraldehyde, aldol, glyoxal, terephthalaldehyde, benzaldehyde, 30 o-fluorobenzaldehyde, a,a,a,-trifluoro-m-tolualdehyde, pentafluorobenzaldehyde, m-bromobenzaldehyde, 3,5-diiodo-4-hydroxybenzaldehyde, o-chlorobenzaldehyde, 3,5-dichlorobenzaldehyde, 3,5-dichlorosalicylal- dehyde, 2-chloro-6-fluorobenzaldehyde, 2,3,6-trichlorobenzaldehyde, 2,5-dichloro-4-nitrobenzaldehyde, 2,4,5-trichloro-3-nitrobenzaldehyde, salicylaldehyde, 5-bromosalicylaldehyde, vanillin, 2-carboxybenzal- dehyde, 5-chlorosalicylaldehyde, p-methylthiobenzaldehyde, 4-hydroxy-3,5-dimethoxybenzaldehyde, 3- 35 ethoxy-4-hydroxybenzaldehyde, 5-nitrosalicylaldehyde, 4-hydroxy-3,5-di-tert-butylbenzaldehyde, p-anisal- dehyde, 2,5-dimethoxybenzaldehyde, m-[m-(trifluoromethyl)phenoxy]benzaldehyde, 5-bromo-o-anisal- dehyde, 3-chloro-4-hydroxy-5-ethoxybenzaldehyde, 4-hydroxy-5-bromo-m-anisaldehyde, o-ethoxybenzal- dehyde, 2,3-dimethyl-4-methoxybenzaldehyde, 4-[j8-(diethylamino)ethoxy]benzaldehyde, piperonal, 6- nitropiperonal, 3-methyl-p-anisaldehyde, m-(p-chlorophenoxy)benzaldehyde, 3-benzyloxybenzaldehyde, p- 40 phenoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, methyl 4-formylbenzoate, o-nitrobenzaldehyde, p- nitrobenzaldehyde, 4-chloro-3-nitrobenzaldehyde, 3-methoxy-2-nitrobenzaldehyde, 4-fluoro-2-nitrobenzal- dehyde, 5-hydroxy-2-nitrobenzaldehyde, p-cyanobenzaldehyde, 2,4-dimethylbenzaldehyde, o-tolualdehyde, cuminaldehyde, a-naphthaldehyde, p-phenylbenzaldehyde, p-dimethylaminobenzaldehyde, 5-formyl-2-furan- sulfonic acid, p-acetaminobenzaldehyde, 5-methylfurfural, 2-thiophenecarboaldehyde, /3-2-furylacrolein 45 nicotinaldehyde, furfural, 5-nitrofurfural, 5-methyl-2-thiophenecarboaldehyde, N-methylpyrrole-2-carboal- dehyde, chloroacetone, bromoacetone, hydroxyacetone, a,a'-dichloroacetone, hexachloroacetone, methyl ethyl ketone, methyl vinyl ketone, diacetyl, 3-chloro-2-butanone, cyclobutanone, acetoin, methoxyacetone, perchloro-2-cyclobuten -1-one, 3-methyl-2-butanone, 2-pentanone, cyclopentanone, 3-penten -2-one, ac- etylacetone, pinacolone, bromopinacolone, 3-hexanone, mesityl oxide, 4-methyl-2-pentanone, ac- 50 etonylacetone, cyclohexanone, 1 ,2-cyclohexanedione, 1 ,4-cyclohexanedione, 2-cyclohexen -1-one, 3- methyl-2-cyclopenten -1-one, 3-methylcyclopentanone, 2-methyl-1 ,3-cyclopentanedione, 3-acetylfuran, 1- hexen -5-one, 2-hydroxy-3-methyl-2-cyclopenten -1-one, methyl 1-methylcyclopropyl ketone, 2-methyl- cyclohexanone, 2-methyl-1 ,3-cyclohexanedione, 5-methyl-2-hexanone, 2-heptanone, dimedone, 2-octanone, 2-methyl-2-hepten -6-one, 3,5-dimethyl-2-cyclohexen -1-one, isophorone, phorone, 2,6-dimethyl-4-hep- 55 tanone, 4-tert-butylcyclohexanone, menthone, i-carvone, 0-ionone, DL-camphor, 6-methoxy-1 -tetralone, 6- undecanone, 5-nonanone, quinone, di-tert-butyl-p-quinone, 2,5-dichloro-p-benzoquinone, 2,3-dichloro-1 ,4- naphthoquinone, 2-hydroxy-1 ,4-naphthoquinone, 2-methyl-1 ,4-naphthoquinone, anthraquinone, phenanth- renequinone, 2,6-dihydroxyanthraquinone, acetophenone, o-hydroxyacetophenone, p-nitroacetophenone, m-

43 EP 0 128 006 B1

chloroacetophenone, o-fluoroacetophenone, p-bromoacetophenone, 2,4-dichloroacetophenone, 2,4-dihydrox- yacetophenone, a,a-dichloroacetophenone, a-bromoacetophenone, 2,3,4-trichloroacetophenone, a- chloroacetophenone, p-methoxyacetophenone, o-methylacetophenone, a,a,a-trifluoroacetophenone, p- chlorophenacyl bromide, a-methoxyacetophenone, propiophenone, p-chloropropiophenone, p- 5 fluoropropiophenone, 2-hydroxy-5-methylacetophenone, phenoxyacetone, 1-indanone, 1,3-indanedione, phe- nyl n-propyl ketone, a-bromoisobutyrophenone, phenyl propenyl ketone, o-hydroxybutyrophenone, ben- zoylacetone, 3,4-dimethylacetophenone, cyclopropyl phenyl ketone, benzalacetone, 4-methox- ypropiophenone, 2,4,6-trimethylacetophenone, valerophenone, /3-acetonaphthone, hexaphenone, 2-acetyl-1- tetralone, benzophenone, p-chlorobenzophenone, 2-chloro-5-nitrobenzophenone, 4-hydroxybenzophenone, w 2,4-dihydroxybenzophenone, 5-chloro-2-hydroxybenzophenone, 9-fluorenone, benzoyl, benzil, deoxyben- zoin, 4-acetylbiphenyl, p-phenyl-a-bromoacetophenone, acridone, 4-methoxy-2-hydroxybenzophenone, anth- rone, dibenzoylmethane, benzalacetophenone, 2-hydroxychalcone, tetrahydrothiopyran -4-one, bis-3,4- methylenedioxybenzil, 2,2'-dihydroxy-4,4'-dimethoxylbenzophenone, 2'-carboxy-2-hydroxy-4-methoxyben- zophenone, 2'-(o-chlorobenzoyl)-2,4'-dichloroacetaniIide, 4,4'-bis(dimethylamino)benzophenone, 5,7-dich- 75 loroisatin, 6-chloroisatin, isatin, 5-nitroisatin, 3-(hexahydro-1H-azepin-1-yl)-3'-nitropropiophenone, s-triazolo- [4,3,a]pyrido-3(2H)-one, perinaphthenone, thioxanthen -9-one, xanthone, 2-acetylpyridine, 3-benzoyIpyridine, di-2-pyridyl ketone, di-pyridylglyoxal, 3,5-diiodo-4-pyridone, 3-acetyl-2,4-dimethylpyrrole, pyrrole-2-carboal- dehyde, 2,2,6,6-tetramethyl-4-piperidone, 1-methyl-4-piperidone, methyl 4-oxo-3-piperidinecarboxylate and the like. 20 The solvent used in this method (k) includes for example aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, etc., aromatic hydrocarbons such as benzene, toluene, xylene, etc., halogenated hydrocarbons such as chloroform, carbon tetrachloride dichloroethane, chlorobenzene, dich- lorobenzene, etc., ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, diethylene glycol dimethyl ether, etc., alcohols such as methanol, ethanol, isopropanol, tert-butanol, octanol, cyclohexanol, 25 methyl cellosolve, diethylene glycol, glycerin, etc., esters such as ethyl formate, ethyl acetate, butyl acetate, diethyl carbonate, etc., nitro compounds such as nitroethane, nitrobenzene, etc., nitriles such as acetonitrile, isobutyronitrile, etc., tertiary amines such as pyridine, triethylamine, N,N-diethylaniline, tributylamine, N- methylmorpholine, etc., acid amides such as formamide, N,N-dimethylformamide, acetamide, etc., sulfur compounds such as dimethyl sulfoxide, sulfolane, etc., water and mixtures thereof. 30 The catalyst used includes for example benzenesulfonic acid, p-toluenesulfonic acid, phosphoryl chloride, boron trifluoride, titanium tetrachloride and the like. After completion of the reaction, the common after-treatment is carried out and if necessary, the product obtained is purified by chromatography, distillation, recrystallization and the like. Next, examples of production of the present compound by the method (k) will be shown. 35 Production Example 15

A mixture of 2-cycloheptenylamine (11.1 g, 0.1 mole), benzaldehyde (10.6 g, 0.1 mole) and benzene (50 ml) was heated under reflux, and resulting water was removed by azeotropic distillation. The mixture 40 was concentrated to obtain 16.7 g of N-benzylidene-2-cycloheptenylamine [Compound (280)].

n^2"3 1.5631

45

Production example 16

A mixture of 2-cyclohexenylamine (9.7 g, 0.1 mole), cyclohexanone (9.8 g, 0.1 mole), zinc chloride (0.16 so g) and benzene (50 ml) was heated under reflux, and resulting water was removed by azeotropic distillation. The mixture was concentrated and distilled to obtain 12.4 g of N-cyclohexylidene-2-cyclohexenylamine [Compound (344)] b.p. 91-93° C/2 mmHg Some of the present compounds which can be produced by this method are shown in Table 4. 55

44 EP 0 128 006 B1

Table 4

Present compounds represented by the formula,

,x

10 Compound n4 5 . No R R n Physical constant

(278) H /r\ 2 n24"1 1.5135 -fJ-CF D 15

(279) H /=^ 3 n23"7 1.5476 F D

20 (280) H -f~\ 3 - n22"3 1.5631 * f • L)

(281) H -CH2CH(CH3)CH CH - 3 ^'^ 1-4876 25 CH=C(CH3)2

(282) H Yh \ 3 nQ5'3 1-5004

30 (283) H -CH2CH3 3 "q3*0 1-4823

(284) H ~CH2CH2 \_7 3 nD3*5 1*5406 35

(285) H -^ / 3 no4'2 i-5855

40 (286) H -/ \ 3 np4'2 1-5637 N

(287) H LiJ 3 nn5"3 1-6192

45 (288) H -Q-G 3 nD4"2 i'6279

50

55

45 EP 0 128 006 B1

Compound r4 r5 n Physlcal constant

(289) H -CH2CH2CH2CH3 3 n24'3 1.4797

(290) H -CH2OCH3 3 n24'0 1.4916 9 (29D H -CH(CH3)2 3 n23 " 1.4785 70 <292> H ~y/ 3 n23"5 US792 OH

(293) H -CC1=CH-^ 3 n24"2 1.5869 75

(294) H -CH=CH-Q 3 n24"2 1.5994

20 (295) H -CHC-Q 3 n23'0 1.5919

(296) H -Q-CH=N-<^) 3 m.p. 114-115°C 25 <297> H -Q 3 n21-5 1.5589

CH3

30 O <298' H 3 n21-9 1.5532

OC2H5 (299) H n22"2 35 -Q> 3 1.5502

<300> H -f\sCH^ 3 m.p. 42CC

40 (301) H y=> 3 n23;5 1.5725 NO2

(302) H -Q-CN n24"1 45 3 1.5769

50

55

46 EP 0 128 006 B1

Compound Physical constant No.

(303) n^3'6 1.5488 -Q. rr>

(304) -CH2CH2CH2CH2CH2- b.p. 79-83 C/0-75 mmHg 10 23.6 (305) "D 1.5116 CF. 75 23 9 (306) -COOCH. n^ 1.5640

(307) -CH2CH3 b.p. 111-114 C/1.2mmHg 20 CH =CH- (308) -CH2C (CH3) CICHJ b.p. 103-106eC/0.8mmHg

(309) ■o n2D7-0 1.5692 25

(310) n"-5 1.5672

CH- 30

(311) nl1-1 1.5839

OH 35 (312) n^6-8 1.5519

40 (313) n^5*4 1.5610 OC2H5

o»a n^4'9 1.5941 45 (314)

(315) ul5-0 1.5951

50

55

47 EP 0 128 006 B1

Compound R4 5 „ Physical constant No .

(316) H ~{3~CN 2 n25'3 L5850

(317) H -/"^ 2 n25'0 1.5680 \=N D 10 13181 " CO 2 "d5'° 1-6300

-0 (319) H Y 2 n26"0 75 D 1.5661 CH3

(320) H -/_Vn{CH ) 2 m.p. 78.7°C

20 (321) H Tl-C5Hn 2 no3'7 1-4856

(322) H -C(C2H5)=CHCH3 2 "q7"3 1-5021

25 (323) H -(h\ 2 n^7-0 1.4990

(324) H -CH2CH2-/^ 2 n25'0 1.5620

30 ° (325) H -CH2OCH3 2 n" " 1.5029

(326) H -(^y 2 n^5-2 1.5185

35 (327) H JT} 2 n25-5 1.5560 o

(328) H -CH=CH-^~^ 2 n25 • 8 1.6050 40

(329) H "(IVSCH3 2 nD4'" 1-6121

-f\ 45 (330) H 2 n24"0 1.5116

50

55

48 EP 0 128 006 B1

_5 constant Compound _4 R n Physical No. R

{331) H _/~"\_0H 2 m-P- 140. 3*C

OC2H5

(332) H -Q 2 "d5*3 I<511° 70 /CF3 °-O

(333) H -f~\~OCH2 2 n^5'3 1.5750 75 /"\ CH3 CH3

(334) H "O~^3 2 m'P" 95-6CC 20

(335) H -/~\-CH=N-/) 2 m.p. 97-100cC

25 (336) H -CC1=CH-Q 2 n^6"2 1.6123

(337) H -( A 2 nD4"5 K5858 =■ S CH3 30 2 ^^ (338) H j-V 2 n2b-2 1.5945

35 (339) H -f"V-° 2 n25-1 1.6070

NO2

40 (340) H -Q 1 n24'0 1.5686

(341) H -^^ 4 n^5-2 1.5600 45 (342) H -C5C-Q 2 nD7'5 1-59U

50

55

49 EP 0 128 006 B1

Compound R4 r5 „ Physical constant

s Br

(343) H -O-°C2H5 2 "d°"8 i-seae

OC2H5 10 (344) • -CH2CH2CH2CH2CH2- 2 C.A. 8£, 49759k

75 Method (£) :

When the present compound is the salt of the amine compound represented by the foregoing formula (V), provided that when both R6 and R7 are a hydrogen atom, salts with the following acids are excluded for 20 each value of n : when n is 1, hydrochloric acid, picric acid; when n is 2, hydrochloric acid, hydrobromic acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, (2-cyclohex- enylamino)methanesulfonic acid, (3-cyclohexenylamino)methanesulfonic acid, acetic acid, lactic acid, suc- cinic acid, fumaric acid, maleic acid, malic acid, tartaric acid, citric acid, ascorbic acid, benzoic acid, salicylic acid, phenylacetic acid, mandelic acid, 4,4'-methylenebis(3-hydroxy-/3-naphthoic acid); when n is 3, 25 hydrochloric acid; and when n is 4, picric acid, the present compound can be produced by reacting an amine compound represented by the formula (V) with an acid of 0.95 to 1 .0 equivalent based thereon at -10° to 80° C for preferably 0.5 to 1 hour. The acid described above includes for example inorganic acids, organic acids (e.g. organic sulfonic acids, organic sulfinic acids, organic phosphoric acids, substituted or non-substituted aliphatic, aromatic or 30 heteroaromatic carboxylic acids, substituted or non-substituted aliphatic polyhydric carboxylic acids or aromatic dicarboxylic acids, phenols and substituted or non-substituted dithiocarbamic acids, etc.), Lewis acids, etc. More specifically, the inorganic acids include for example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, sulfurous acid, nitric acid, nitrous acid, phos- 35 phorous acid, perchloric acid, chloric acid, chlorous acid, iodic acid, bromic acid, arsenic acid, carbonic acid, selenium hydride, tellurium hydride, phosphonic acid, hypophosphoric acid, diphosphonic acid, pyrophosphoric acid, metaphosphoric acid, polyphosphoric acid, selenic acid, selenious acid, telluric acid, tellurous acid, arsenious acid, antimonic acid, antimonous acid, borofluoric acid, etc. Of the organic acids, the organic sulfonic acids include for example hydroxymethanesulfonic acid, trifluoromethanesulfonic acid, 40 £-bromoethanesulfonic acid, allylsulfonic acid, 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid, D-10-camphorsulfonic acid, benzenesulfonic acid, m-nitrobenzenesulfonic acid, m-benzenedisulfonic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, 2-(cyclohexenylamino)- methanesulfonic acid, (3-cyclohexenylamino)methanesulfonic acid, p-ethylbenzenesulfonic acid, a-naph- thalenesulfonic acid, /3-naphthalenesulfonic acid, p-toluenesulfonic acid, p-chloromethylbenzenesulfonic 45 acid, p-phenolsulfonic acid, 2-pyridylhydroxymethanesulfonic acid, 2,6-naphthalenedisulfonic acid, etc.; the organic sulfinic acids include for example benzenesulfinic acid, p-toluenesulfinic acid, etc.; the organic phosphoric acids include for example phenylphosphonous acid, butylphosphonous acid, methylphosphon- ous acid, dibenzenephosphinic acid, dibutylphosphinic acid, benzenephosphonic acid, methylphosphonic acid, phenylphosphinic acid, methylphosphinic acid, dibenzenethiophosphinic acid, dibutylthiophosphinic 50 acid, benzenethiophosphonic acid, methylthiophosphonic acid, phenylthiophosphinic acid, methyl- thiophosphinic acid, benzenethiophosphonous acid, dibutylthiophosphonous acid, diethyl dithiophosphate, a- hydroxybenzylphosphonous acid, toluenephosphonous acid, etc.; the substituted or non-substituted aliphatic carboxylic acids include for example mandelic acid, acetic acid, lactic acid, ascorbic acid, phenylacetic acid, bromoacetic acid, trichloroacetic acid, chlorodifluoroacetic acid, thioacetic acid, glycolacetic acid, 55 glyoxylic acid, acrylic acid, /3-chloroacrylic acid, cyanoacetic acid, ethoxyacetic acid, /3-chloropropionic acid, perfluoropropionic acid, propiolic acid, n-butyric acid, isobutyric acid, a-hydroxyisobutyric acid, crotonic acid, mucochloric acid, cyclopropanecarboxylic acid, isovaleric acid, 1 -methylcyclopropanecarboxylic acid, 1-cyanocyclopropanecarboxylic acid, cyclobutanecarboxylic acid, cyclopentanecarboxylic acid, 2-

50 EP 0 128 006 B1

ketobutyric acid, levulinic acid, pivalic acid, tert-butylacetic acid, coumarinic acid, 3-cyclohexenecarboxylic acid, /3-2-furylacrylic acid, 3-pyridylacetic acid, phenylthioacetic acid, m-chlorophenylacetic acid, o- nitrophenylacetic acid, p-fluorophenylacetic acid, o-hydroxyphenylacetic acid, phenoxyacetic acid, o- chlorophenoxyacetic acid, 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, cyclohex- 5 ylacetic acid, 1-methyl-1-cyclohexanecarboxylic acid, 6-acetamidohexanoic acid, heptylic acid, di-terebic acid, benzoylformic acid, cinnamic acid, o-chlorocinnamic acid, 2,4-dichlorocinnamic acid, m-nitrocinnamic acid, o-hydroxycinnamic acid, di-2-phenoxypropionic acid, 3-phenoxypropionic acid, 3-phenylpropionic acid, 3-(p-hydroxyphenyl)propionic acid, 2-(2,4,5-trichlorophenoxy)propionic acid, 4-methoxyphenylacetic acid, p-chloro-2-methylphenylacetic acid, 3,4-methylenedioxyphenylacetic acid, 4-chloro-2-methylphenox- w yacetic acid, m-tolylacetic acid, a,a,a-trifluoro-m-tolylacetic acid, p-hydroxyphenylpyruvic acid, a-cyanocin- namic acid, p-methoxycinnamic acid, m-trifluoromethylcinnamic acid, 3,4-methylenedioxycinnamic acid, 3,4- dimethoxyphenylacetic acid, (-)-a-methoxy-a-trifluoromethylphenylacetic acid, 1 ,4-benzdioxane-6-acetic acid, 3-phenyl-n-butyric acid, 1-phenyl-1-cyclopropanecarboxylic acid, 2-(p-methoxyphenyl)-acetylene-1- carboxylic acid, 3-benzoylpropionic acid, 2-(p-chlorophenoxy)-2-methylpropionic acid, a-naphthylacetic acid, 75 #-naphthoxyacetic acid, 3,4,5-trimethoxyphenylacetic acid, diphenylacetic acid, bis(p-chlorophenyl)acetic acid, l-menthoxyacetic acid, diphenyleneacetic acid, 1-phenylcyclopentanecarboxylic acid, 1-(p- chlorophenyl)-1-cyclopentanecarboxylic acid, dt-3-camphorcarboxylic acid, palmitic acid, stearic acid, ben- zilic acid, desoxycholic acid, linolic acid, oleic acid, a-acetamidocinnamic acid, etc.; the aromatic carboxylic acids include for example benzoic acid, salicylic acid, o-toluic acid, a,a,a-trifluoro-m-toluic acid, p- 20 ethylbenzoic acid, 2,6-dimethylbenzoic acid, 2,4,6-trimethylbenzoic acid, p-tert-butylbenzoic acid, p- bromomethylbenzoic acid, 2-biphenylcarboxylic acid, 44'-methylenebis(3-hydroxy-^-naphthoic acid), a- naphthoic acid, p-benzoylbenzoic acid, phthalamic acid, o-phthalaldehydic acid, m-nitrobenzoic acid, 3,4- dinitrobenzoic acid, m-cyanobenzoic acid, thiosalicylic acid, gallic acid, m-hydroxybenzoic acid, 2,3- dihydroxybenzoic acid, 1 -hydroxy-2-naphthoic acid, o-anisic acid, 3,4-dimethoxybenzoic acid, 4-hydroxy-3- 25 methoxybenzoic acid, 4-hydroxy-3,5-dimethoxybenzoic acid, 4-n-butoxybenzoic acid, 3-phenoxybenzoic acid, piperonylic acid, o-acetamidobenzoic acid, p-chlorobenzoic acid, 3,5-dichlorobenzoic acid, o- fluorobenzoic acid, m-fluorobenzoic acid, 2,6-difluorobenzoic acid, 2,6-dichlorobenzoic acid, 2,3,5- triiodobenzoic acid, 4-chlorosalicylic acid, 3-nitrosalicylic acid, 5-bromosalicylic acid, 2-chloro-3-nitrobenzoic acid, 3-chloro-4-hydroxybenzoic acid, 3,5-dichioro-4-hydroxybenzoic acid, 3-chloro-4-methylbenzoic acid, 3- 30 methoxy-4-nitrobenzoic acid, 3-methoxy-4-hydroxybenzoic acid, 3-methoxy-4-methylbenzoic acid, 3-methyl- 2-nitrobenzoic acid, 3-hydroxy-4-nitrobenzoic acid, 3,5-di-tert-butyl-4-hydroxybenzoic acid, o-thymotinic acid, etc.; the heteroaromatic carboxylic acids include for example N-methylpyrrole-2-carboxylic acid, 2- furancarboxylic acid, 5-bromo-2-furancarboxylic acid, pyrrole-2-carboxylic acid, 3-furancarboxylic acid, nico- tinic acid, isonicotinic acid, citrazinic acid, a-picolinic acid, etc.; the substituted or non-substituted aliphatic 35 polyhydric carboxylic acids include for example succinic acid, fumaric acid, maleic acid, malic acid, tartaric acid, citric acid, oxalic acid, malonic acid, ethylmalonic acid, hydroxymalonic acid, methylsuccinic acid, 2- methyl-2-phenylsuccinic acid, 2-ethyl-2-methylsuccinic acid, 2-isopropylsuccinic acid, bromosuccinic acid, 2,3-dibromosuccinic acid, a-ketoglutaric acid, 3-ethyl-3-methylglutaric acid, glutaconic acid, itaconic acid, mesaconic acid, citraconic acid, adipic acid, camphoric acid, diglycollic acid, acetylenedicarboxylic acid, 40 dimethyicyclopropanedicarboxylic acid, etc.; the aromatic dicarboxylic acids include for example phthalic acid, isophthalic acid, terephthalic acid, homophthalic acid, 3-nitrophthalic acid, 4-hydroxyisophthalic acid, tetrachlorophthalic acid tetrachloroterephthalic acid, nitroterephthalic acid, pyrazine-2,3-dicarboxylic acid, o- phenylenediacetic acid, 5,5'-methylenedisalicylic acid, etc.; the phenols include for example picric acid, 2,4- dinitrophenol, 2,6-dinitrophenol, 2,6-diiodo-4-nitrophenol, 2,6-dichloro-4-nitrophenol, 2,5-dichloro-4- 45 nitrophenol, 2,6-dibromo-4-nitrophenol, 2-bromo-4-chloro-6-nitrophenol, 2,4-dichloro-6-nitrophenol, etc.; and the substituted or non-substituted dithiocarbamic acids include for example 2-cyclohexenyldithiocarbamic acid, 2-cycloheptenyldithiocarbamic acid, methyldithiocarbamic acid, dimethyldithiocarbamic acid, ethylenebis(dithiocarbamic acid), etc. Further, the Lewis acid includes for example boron trifluoride, boron trichloride, boron tribromide, aluminum fluoride, aluminum chloride, aluminum bromide, aluminum iodide, 50 aluminum sulfate, iron fluoride, iron chloride, iron bromide, iron nitrate, iron sulfate, gallium fluoride, gallium chloride antimony fluoride, antimony chloride, antimony sulfate, indium fluoride, indium chloride, tin fluoride, tin chloride, tin bromide, tin iodide, arsenic fluoride, arsenic chloride, zinc fluoride, zinc chloride, zinc bromide, zinc iodide, copper chloride, barium chloride, silver chloride, etc. The solvent used in the foregoing method includes for example aliphatic hydrocarbons such as hexane, 55 heptane, ligroin, petroleum ether, etc., aromatic hydrocarbons such as benzene, toluene, xylene, etc., halogenated hydrocarbons such as chloroform, carbon tetrachloride dichloroethane, chlorobenzene, dich- lorobenzene, etc., ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, diethylene glycol dimethyl ether, etc., ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone,

51 EP 0 128 006 B1

cyclohexanone, etc., alcohols such as methanol, ethanol, isopropanol, tert-butanol, octanol, cyclohexanol, methyl cellosolve, diethylene glycol, glycerin, etc., esters such as ethyl formate, ethyl acetate, butyl acetate, diethyl carbonate, etc., nitro compounds such as nitroethane, nitrobenzene, etc., nitriles such as acetonitrile, isobutyronitrile, etc., sulfur compounds such as dimethyl sulfoxide, sulfolane, etc., water, and mixtures 5 thereof. Next, examples of production of the present compound by the method (I) will be shown.

Production example 17

io Cone, hydrochloric acid (10.1 g) was added dropwise to a mixture of 2-cycloheptenylamine (11.1 g, 0.1 mole) and isopropyl alcohol (24 g) with stirring and ice-cooling. The reaction mixture was concentrated under reduced pressure, and the deposited crystal was washed with diethyl ether and dried to obtain 14 g of 2-cycloheptenylamine hydrochloride [Compound (349)]. m.p. 174-176° C 75 Production example 18

To a solution of phenylphosphinic acid (0.72 g, 10 mmoles) in isopropyl alcohol (2.4 g) was added dropwise 2-cycloheptenylamine (0.56 g, 10 mmoles) with stirring and ice-cooling. The reaction mixture was 20 concentrated under reduced pressure, and the deposited crystal was washed with diethyl ether and dried to obtain 1.2 g of the phenylphosphinic acid salt of 2-cycloheptenylamine [Compound (353)]. m.p. 171-174° C Some of the present compounds which can be produced by this method are shown in Table 5 by means of corresponding acids. 25

30

35

40

45

50

55

52 EP 0 128 006 B1

Table 5

Salts of the 2-cycloalkenylamine derivative represented by the formula,

X 10

Compound 1 2 n Acid Physical 75 No. constant

{345) H CH 3 Hydrochloric acid m.p. 125CC (346) H H 1 — C.A. 81, 115149v

20 (347) H H 3 — Ann. 317, 243(1901)

(348) H H 4 C.A. 5_8_, 9005a (349) H H 3 Hydrochloric acid Ann. 317,243 (1901)

25 (350) H H 1 Hydrochloric acid C.A. 56, 2341b

(351) H H 4 Hydrochloric acid m.p. 271eC (352) H H 1 Picric acid C.A.56, 2341b

30 (353) H H 3 Phenylphosphinic m.p. 171-174°C acid

(354) H H 3 Methylphosphinic n23-4 i 4901 acid D

35 (355) H H 3 tf-Naphthalene- 23.4 . ,,.„, sulfonic acid nD *-"«l acid (356) H H 3 n-Butyric n23"4 1 4827

40 (357) H H 3 Zinc chloride m.p. 137-144°C (358) H H 3 Ferric chloride m.p. 137-140" C (dec.) (359) H H 3 p-Toluenesulf inic m.p. 156-159CC acid 45 (360) H H 3 3-Chloropropionic m.p. 82-85' C acid

(361) H H 3 Benzoic acid m.p. 167-170°C

50 (362) H H 3 o-Anisic acid m.p. 160-163°C

55

53 EP 0 128 006 B1

1 1 j 1 I . Compound Rl R2 n Acid Physical No- constant

(363) H H 3 2-Furancarboxylic m.p. 187-190eC acid

(364) H H 3 Maleic acid m.p. 100-103°C (365) H h 3 Phthalic acid m.p. 151-154CC 10 (366) H H 1 2,4-Dinitrophenol m.p. 164-166'C (367) H H 3 Acetic acid m.p. 86CC 0 (368) H H 3 CH..CH-P-OH n18"4 1.5076 75 3,| D OH H

(369) H -CH(CH3)CN 3 Pheny lphosphinic m.p. 95*'c acid

20 (370) H -CH(CH3)CN 3 Methy Iphosphir.ic n22.0 dC 1Q D 1

(371) H -CH2CN 3 Phenylphosphinic m.p. 77°C acid

25 (372) CH3 CK3 3 Hydrochloric acid m.p. 159*0

(373) CH CH 3 Phenylphosphinic 23.6 , ., „ J J acid nD 1-5389

(374) CH3 H 3 Phenylphosphinic n23'5 30 1 540o

When the present compounds thus obtained are used as the active ingredient of soil disease-controlling agents, they may be used as such without adding any other components, but generally, they are formulated 35 into emulsifiable concentrates, wettable powders, suspension formulations, granules, dusts, water-soluble formulations, fine granules and the like by mixing with solid carriers, liquid carriers, surface active agents and other auxiliaries for formulation. These formulations contain the present compound as an active ingredient in amounts of 0.1 to 99.9%, preferably 0.2 to 80.0% by weight ratio. 40 The above solid carrier includes for example the fine powders or granules of kaolin clay, attapulgite clay, bentonite, terra abla, pyrophyllite, talc, diatomaceous earth, calcite, corn stalk powder, walnut shell powder, urea, ammonium sulfate, synthetic hydrated silicon dioxide, etc. The liquid carrier includes for example aromatic hydrocarbons (e.g. xylene, methylnaphthalene), alcohols (e.g. isopropanol, ethylene glycol, cellosolve), ketones e.g. acetone, cyclohexanone, isophorone), vegetable oils (e.g. soybean oil, 45 cotton seed oil), dimethyl sulfoxide, acetonitrile, water and the like. As the surface active agent used for emulsification, dispersion, wetting, etc., there are given for examples anionic surface active agents such as the salt of alkyl sulfate, alkyl(aryl) sulfonates, dialkyl sulfosuccinates, the salt of the phosphoric acid ester of polyoxyethylene alkylaryl ether, naphthalenesulfonic acid/formalin condensates, etc. and nonionic surface active agents such as polyoxyethylene alkyl ether, 50 polyoxyethylene polyoxypropylene block copolymers, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, etc. The auxiliary for formulation includes for example lignosulfonates, alginates, polyvinyl alcohol, gum arabic, CMC (carboxymethyl cellulose), PAP (isopropyl acid phosphate) and the like. Next, formulation examples will be shown. The present compounds are shown by Compound No. in Tables 1 to 5. Parts in the examples are by weight. 55 Formulation example 1

Two parts of the compound (2), 88 parts of kaolin clay and 10 parts of talc are thoroughly mixed while

54 EP 0 128 006 B1

being powdered to obtain a dust.

Formulation example 2

5 Two parts of the compound (4), 1 part of synthetic hydrated silicon dioxide, 2 parts of calcium lignosulfonate, 30 parts of bentonite and 65 parts of kaolin clay are thoroughly mixed while being powdered, well kneaded with water, granulated and then dried to obtain a granule.

Formulation example 3 w Fifty parts of the compound (123), 3 parts of calcium lignosulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic hydrated silicon dioxide are thoroughly mixed while being powdered to obtain a wettable powder.

75 Formulation example 4

Ten parts of the compound (217), 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate, 30 parts of xylene and 40 parts of isopropanol are thoroughly mixed to obtain an emulsifiable concentrate. 20 Formulation example 5

Thirty parts of the compound (280) is dissolved in dimethyl sulfoxide, and the resulting solution is adsorbed in 70 parts of attapulgite clay. The clay impregnated with the solution is then dried to obtain a fine 25 granule.

Formulation example 6

Ten parts of the compound (349), 1 part of polyoxyethylene styrylphenyl ether and 89 parts of water 30 are mixed to obtain a water-soluble formulation. These formulations, either as such or as aqueous dilute liquors, are used in foliar treatment or soil treatment. In the case of soil treatment, the formulations are sprayed (or scattered) onto soil surface [as need arises, they are mixed with the soil after spraying (or scattering)], or the soil is drenched with them. Also, an increase in the controlling effect can be expected by using them in mixture with other soil disease- 35 controlling agents. Further, these formulations may also be used in mixture with other fungicides, soil insect pest controlling agents, nematocides, plant growth regulating agents, fertilizers, soil improvers and the like. When the present compound is used as the active ingredient of soil disease controlling agents, its dosage rate is generally 0.001 to 50 kg per 10 ares, preferably 0.01 to 10 kg per 10 ares. The granule, dust, fine granule, etc. are used as such without dilution, and when the emulsifiable 40 concentrate, wettable powder, suspension formuation, water-soluble formulation, etc. are used as aqueous dilute liquors, their application concentration is 0.0005 to to 5.0%, preferably 0.005 to 0.5%. Next, that the present compound is useful as the active ingredient of soil disease controlling agents will be illustrated with reference to the following test examples. Hereupon, the present compounds are shown by Compound No. in Tables 1 to 5, and compounds used as a control are shown by Compound symbol in 45 Table 6.

50

55

55 EP 0 128 006 B1

Table 6

Compound Chemical structure Remark symbol

CONHC4Hg-n Benomyl (commercial «*=*^VNv fungicide) A 10 UN>NHC0°CH3

B CC13NO2 Chloropicrin (commercial fumigant) 75

-OH Hydroxyisoxazole { C / \j commercial fungicide) U 20 H3C

Cl Cl \ / PCNB (commercial 25 D C1 °2 fungicide) \ /

Cl Cl

30

The controlling effect is indicated by the numerical value of the percentage of healthy seedlings obtained as follows : The condition of disease of test plants on examination, i.e. the degrees of the colony and symptom on the 35 leaves, stems, roots, etc. of the test plants are observed with the naked eye; the number of test plants showing no colony nor symptom at all (hereinafter referred to as number of healthy seedlings) is counted for each case described below : A case wherein the compound was applied (hereinafter referred to as number of healthy seedlings in treated plot) and another case wherein neither application of the compound nor inoculation of pathogens was carried out (hereinafter referred to as number of healthy seedlings in 40 untreated and uninoculated plot); and the percentage of healthy seedlings (%) is obtained from the following equation :

Percentage of Number of healthy seedlings in 45 healthy seedlings treated plot X loo Number of healthy seedlings in untreated and uninoculated plot

50 Test example 1 Controlling effect against yellows of Japanese radish (Fusarium oxysporum f.sp.raphani)

A plastic pot was filled with a well mixed soil of field soil and infested soil containing cultured Fusarium oxysporum f.sp. raphani, and the seed of radish (variety, Wase-40 nichi) was sowed at a rate of 15/pot and 55 covered with soil. Thereafter, a prescribed amount of each test compound in the form of wettable powder- formulated according to Formulation example 3 was diluted with water and applied to soil drenching. After three weeks' cultivation in a greenhouse, the controlling effect was examined. The results are shown in Table 7.

56 EP 0 128 006 B1

Table 7

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient (g/lOare) lings (%) (1) 300 100.0 (2) " 100.0 " 10 (3) 100.0 (4) " 100.0 (5) " 100.0 (6) M 100.0 (7) - 75 100.0 (8) " 100.0 (9) " 100.0 (10) " 100.0 - (11) " 100.0 20 (12) M 100.0 (13) " 100.0 (14) " 100.0 (15) M 100.0 25 (16) " 100.0 (17) " 100.0 (18) " 100.0 (19) " 100.0 30 (20) " 100.0 (21) " 100.0 (22) " 100.0 (23) " 100.0 35 (24) » 100.0 (25) " 100.0 (26) " 100.0 (27) " 100.0 40 (28) " 100.0 (29) " 100.0 (30) - 100.0 (31) " 100.0 45 (32) " 100.0 (33) " 100.0 (34) " 100.0 (35) " 100.0 50 (36) " 100.0

55

57 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (t) (37) 300 100.0 (38) " 100.0 (39) " 100.0 (40) » 100.0 (41) - 100.0 10 (42) » 100.0 (43) » 100.0 (44) « 100.0 - (45) « 100.0 75 (46) " 100.0 - (47) - 100.0 (48) - 100.0 (49) M 100.0 - 20 (50) loo.O (51) " 100.0 (52) ■■ 100.0 (53) ■• 100.0 (54) " 100.0 25 (55) " 100.0 (56) " 100.0 (57) » 100.0 (58) » 100.0 30 (59) " 100.0 (60) " 100.0 (61) . " 100.0 (62) " 100.0 (63) " 100.0 35 (64) " 100.0 (65) « 100.0 (66) " 100.0 (67) " 100.0 40 (68) " 100.0 (69) " 100.0 (70) " 100.0 (71) " 100.0 45 (72) M 100.0 (73) '• 100.0 (74) " 100.0

50

55

58 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%) (75) 300 100.0 (76) " 100.0 (77) " 100.0 (78) " 100.0 (79) - 10 100.0 (80) - 100.0 (81) " 100.0 (82) " 100.0 (83) M 100.0 75 (84) M 100.0 (85) " 100.0 (86) " 100.0 (87) " 100.0 20 (88) " 100.0 (89) " 100.0 (90) " 100.0 (91) " 100.0 " 25 (92) 100.0 (93) " 100.0 (94) " 100.0 (95) " 100.0 (96) " 100.0 30 (97) " 100.0 (98) " 100.0 (99) " 100.0 (100) " 100.0 35 (101) " 100.0 (102) " 100.0 (103) " 100.0 (104) " 100.0 40 (105) " 100.0 - (106) " 100.0 (107) » 100.0 (108) " 100.0 (109) " 45 100.0 (110) " 100.0 (HI) " 100.0 (112) " 100.0

50

55

59 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%) (113) 300 100.0 -

50

55

60 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings(%)

(151) 300 100.0 (152) " 100.0 (153) - 100.0 {154) » 100.0 10 (155) - 100.0 (156) " 100-0 (157) " 100.0 (158) " 100.0 " - 75 (159) 100.0 (160) " 100.0 (161) " 100.0 (162) " 100.0 - (163) " 100.0 20 (164) " 100-0 (165) " 100.0 (166) " 100.0 (167) " 100.0 25 (168) " 100-0 (169) " 100.0 (170) " 100.0 (171) •' 100.0 30 (172) " 100.0 (173) " 100-0 (174) » 100.0 (175) - 100.0 " 100.0 35 (176) {177) » 100.0 (178) " 100.0 (179) ■■ 100.0 (180) " 100.0 40 (181) " 100-0 (182) " 100.0 (183) " 100.0 (184) " 100.0 45 (185) " 100.0 (186) " 100.0 (187) " 100.0 (188) " 100.0 50

55

61 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings {%) (189) 300 100.0 (190) - ioo.O (191) " 100.0 (192) - ioo.O 10 (193) - 100.0 (194) - ioo.O (195) " ioo.O (196) • 100.0 75 (197) - ioo.O (198) - ioo.O (199) " 100.0 - (200) " ioo.O (201) " ioo.O 20 (202) ■• ioo.O (203) " ioo.O (204) - ioo.O (205) - ioo.O 25 (206) " 100.0 - (207) - ioo.O (208) " 100.0 - (209) " ioo.O 30 (210) « ioo.O (211) M 100.0 (212) » ioo.O (213) - ioo.O (214) - 35 ioo.O (215) - ioo.O (216) " ioo.O (217) - ioo.O (218) " ioo.O 40 (219) - 100.0 (220) - loo.o (221) - 100.0 <222) - 100.0 45 (223) - ioo.O (224) » 100.0 (225) - ioo.O (226) » ioo.O 50

55

62 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dientfg/lOare) lings (%) (227) 300 100.0 - (228) " 100.0 - (229) " 100.0 - (230) M 100.0 - 10 (231) " 100.0 (232) " 100.0 - (233) " 100.0 (234) " 100.0 " 15 (235) 100.0 (236) " 100.0 (237) " 100.0 '-* (238) " 100.0 (239) " 100.0 - 20 (240) " 100.0 (241) " 100.0 (242) " 100.0 - (243) " 100.0 - 25 (244) " 100.0 (245) " 100.0 (246) " 100.0 (247) " 100.0 30 (248) " 100.0 (249) " 100.0 - (250) " 100.0 - (251) " 100.0 (252) " 100.0 35 (253) " 100.0 (254) n 100.0 (255) " 100.0 - (256) " 100.0 40 (257) " 100.0 (258) " 100.0 - (259) " 100.0 . - (260) " 100.0 45 (261) " 100.0 (262) " 100.0 (263) " 100.0 - (264) " 100.0 50

55

63 EP 0 128 006 B1

™mL, Dos?9e rate of Percentage of compounda Phyto- active ingre- healthy seed- toxicity dient(g/10are) lingsjj) y

(265) 300 ioo.O (266> " 100.0 (267> " 100.0 (268> B 100.0 10 <269> - ioo.O <270> " 100.0 <271> " 100.0 <272> " 100.0 <273> " 100.0 15 <274> - loo.o (275> M loo.o <276> - loo.o <277> " 100.0 20 <278> " 100.0 ^279) " 100.0 (280> " 100.0 <281> " 100.0 25 <282> " 100.0 <283> " 100.0 <284> " 100.0 <285> " 100.0 <286) - 30 100.0 <287> " 100.0 (288> " 100.0 <289» - 100.0 <290> - loo.o 35 <291> " 100.0 (292» - loo.o <293> - ioo.o (294» " 100.0 40 (295> M 100.0 (296» " 100.0 <297> - 100.0 (298> " 100.0 45 (299» " 100.0 (300) " 100.0 <301> " 100.0 (302) " 100.0 50

55

64 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%) (303) 300 100.0 (304) '■ 100.0 (305) " 100.0 (306) " 100.0 (307) - 100.0 10 (308) " 100.0 - (309) " 100.0 (310) " 100.0 (311) " 100.0 75 (312) " 100.0 (313) " 100.0 (314) " 100.0 (315) " 100.0 20 (316) " 100.0 (317) - 100.0 (318) " 100.0 (319) " 100.0 (320) " 100.0 25 (321) " 100.0 - (322) - 100.0 (323) " 100.0 (324) " 100.0 30 (325) " 100.0 (326) " 100.0 (327) " 100.0 - (328) " 100.0 35 (329) " 100.0 (330) " 100.0 (331) " 100.0 - (332) " 100.0 40 (333) " 100.0 (334) " 100.0 . (335) " 100.0 (336) " 100.0 - (337) " 100.0 45 (338) " 100.0 (339) " 100.0 (340) » 100.0

50

55

65 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient (g/lOare) lings (%)

(341) 300 100.0 (342) 100.0 (343) 100.0 (344) 10 100.0 (345) 100.0 (346) 100.0 (347) 100.0 (348) 100.0 75 (349) 100.0 (350) 100.0 (351) 100.0 (352) 100.0 20 (353) 100.0 (354) 100.0 (355) 100.0 (356) 100.0 25 (357) 100.0 (358) 100.0 (359) 100.0 (360) 100.0 (361) 100.0 30 (362) 100.0 (363) 100.0 (364) 100.0 (365) 100.0 35 (366) 100.0 (367) 100.0 (368) 100.0 (369) 100.0 40 (370) 100.0 (371) 100.0 (372) 100.0 (373) 100.0 (374) 45 100.0

50

55

66 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient (g/lOare) lings (%)

A 600 57.8 -

Inoculated and _ 8>9 _ untreated plot 10 Uninoculated and _ jqo q _ untreated plot

75 Test example 2 Controlling effect against yellows of cabbage (Fusarium oxysporum f.sp.conglutinans)

A plastic pot was filled with a uniform mixture of field soil, infested soil containing cultured Fusarium oxysporum f.sp. conglutinans and a prescribed amount of each test compound in the form of fine granule 20 formulated according to Formulation example 5. In this test, chloropicrin was used as follows : After the field soil and infested soil were well mixed and filled in the plastic pot, a prescribed amount of chloropicrin was injected into the soil which was then covered with a polyvinyl chloride film and allowed to stand for one week; thereafter the film was removed and gas release was carried out for one week. The seed of cabbage (variety, Shikidori) was sowed at a rate of 10/pot and covered with soil. After three weeks' cultivation in a 25 greenhouse, the controlling effect was examined. The results are shown in Table 8.

30

35

40

45

50

55

67 EP 0 128 006 B1

Table 8

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%) (1) 300 100.0 - (2) M 100.0 (3) " 100.0 (4) " 100.0 10 (5) " 100.0 (6) " 100.0 (7) M 100.0 (8) M 100.0 75 (95 " 100.0 (10) « 100.0 (ID " 100.0 (12) " 100.0 20 (13) " 100.0 (14) " 100.0 (15) - 100.0 (16) ' M 100.0 (17) " 25 100.0 (18) " 100.0 (19) " 100.0 (20) " 100.0 (21) " 100.0 30 (22) " 100.0 (23) " 100.0 (24) " 100.0 (25) " 100.0 35 (26) n 100.0 - (27) " 100.0 (28) •■ 100.0 (29) - 100.0 40 (30) ■' 100.0 (31) " 100.0 (32) ■■ 100.0 (33) « 100.0 (34) " 100.0 45 (35) " 100.0 (36) " 100.0

50

55

68 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings{%) (37) 300 100.0 (38) " 100.0 - (39) " 100.0 - (40) " 100.0 — (41) " 100.0 10 (42) " 100.0 - (43) n 100.0 (44) " 100.0 — (45) " 100.0 - 75 (46) " 100.0 - (47) " 100.0 +■ (48) " 100.0 - (49) n 100.0 - 20 (50) " 100.0 (51) " 100.0 - (52) " 100.0 (53) " 100.0 - " 100.0 - 25 (54) (55) " 100.0 (56) " 100.0 (57) " 100.0 (58) " 100.0 - 30 (59) " 100.0 (60) " 100.0 - (61) n 100.0 (62) n 100.0 35 (63) " • 100.0 (64) " 100.0 (65) " 100.0 (66) " 100.0 " 40 (67) 100.0 (68) " 100. 0 (69) M 100.0 (70) " 100.0 (71) " 100.0 45 (72) " 100.0 (73) B 100.0 - (74) " 100.0 -

50

55

69 EP 0 128 006 B1

Test Dosage rate of Percentage of Phvto- compound active ingre- healthy seed- toxicitvY dient(g/10are) lings (%) (75> 300 100.0 (76> " 100.0 (77> " 100.0 (78> " 100.0 <79> " 10 100.0 <80> " 100.0 (81» " 100.0 <82> " 100.0 (83> " 100.0 75 <84> " 100.0 (85> " 100.0 <86> " 100.0 (87> " 100.0 20 <88> " 100.0 <89> " 100.0 <90> " 100.0 <91» " 100.0 25 <92> " 100.0 <93» H 100.0 <94> B 100.0 (95> " 100.0 <96> " 30 100.0 {97> " 100.0 (98) " 100.0 <"> " 100.0 (100> " 100.0 35 «101> - loo.o " 100.0 (103> " loo.o <104> " 100.0 40 «!05) » ioo.O {106> " 100.0 (l07> " 100.0 . - {108> " 100.0 (l09» " 45 100.0 (110> " 100.0 " 100.0 50

55

70 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active tngre- healthy seed- toxicity dient(g/10are) lings (%)

(113) 300 100.0 - (114) " 100.0 (115) « 100.0 (116) " 100.0 " 100.0 10 (117) (118) " 100.0 (119) " 100.0 — (120) " 100.0 (12i) - 100.0 15 (122) " 100.0 (123) " 100.0 (124) " 100.0 (125) " 100.0 20 (126) " 100.0 (127) " 100.0 (128) " 100.0 (129) H 100.0 — 25 (130) " I00-0 (131) « 100.0 (132) " 100.0 - (133) ■■ 100.0 (134) " 100.0 30 (135) " I00-0 (136) " 100.0 (137) •• 100.0 (138) " 100.0 - 35 (139) " 100.0 — (140) " 100.0 - (14D ■• 100.0 (142) " 100.0 40 (143) " 100-0 ,144) » 100.0 (145) •• 100.0 (146) " I00-0 •• 100.0 45 {147) (148) " 100.0 - (149) » 100.0 - (150) " 100.0

50

55

71 EP 0 128 006 B1

Test Dosage rate of Percentage of Phy to- compound active ingre- healthy seed- toxicity dtent(g/10are) lings (%) (1S1) 300 100.0 (152) - 100.0 {153) - loo.o (154) - ioo.O C155J - 10 ioo.O (156) - ioo.O (157) " 100.0 (158) - ioo.O (159) " 100.0 75 (160) ■ 100#0 "" d6D " 100.0 + (162) " 100.0 (163) " 100.0 20 <164> " 100.0 d65) " 100.0 (166) - ioo.O (167> "' . 100.0 25 (168) - 100.0 d69> " 100.0 (170) - loo.o (17D - 100.0 (172) " ioo.O 30 (173) - ioo.O (174) « ioo.O (175) " ioo.O (176) " ioo.O 35 (177) •■ ioo.O (178) » ioo.O (179) - ioo.O (180) " 100.0 40 (181) « 100.0 d82) " 100.0 d83) » ioo.O (184) " 100.0 « 45 (185) ioo.O (186) " ioo.O (187) » l00.0 (188) ■• 100.0

50

55

72 EP 0 128 006 B1

Test Posage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%) (189) 300 100.0 (190) " 100.0 (191) " 100.0 - (192) " 100.0 (193) " 100.0 10 (194) " 100.0 - (195) " 100.0 (196) " 100.0 - (197) " 100.0 15 (198) " 100.0 - (199) " 100.0 — (200) " 100.0 - (201) " 100.0 - 20 (202) " 100.0 - (203) " 100.0 - (204) " 100.0 - (205) " 100.0 - (206) " 100.0 - 25 (207) " 100.0 - (208) " 100.0 - (209) " 10C.0 - (210) " 100.0 - 30 (211) " 100.0 (212) " 100.0 (213) " 100.0 (214) " 100.0 35 (215) " 100.0 - (216) " ' 100.0 (217) " 100.0 (218) " 100.0 - " 40 (219) 100.0 - (220) " 100.0 - (221) " 100.0 (222) " 100.0 (223) " 100.0 45 (224) " 100.0 - (225) " 100.0 (226) " 100.0

50

55

73 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (»} (227) 300 100.0 (228) " 100.0 (229) " 100.0 (230) - 100.0 10 (231) - 100.0 (232) " 100.0 (233) • 100.0 (234) " 100.0 75 (235) " 100.0 (236) " 100.0 . - (237) ■' 100.0 (238) " 100.0 " ■ 20 (239) 100.0 - (240) " 100.0 (241) " 100.0 (242) " 100.0 (243) " 100.0 25 (244) " 100.0 (245) - 100.0 (246) " 100.0 (247) " 100.0 30 (248) " 100.0 (249) " 100.0 (250) " 100.0 (251) " 100.0 35 (252) " 100.0 (253) " 100.0 (254) " 100.0 (255) " 100.0 (256) » 100.0 40 (257) " 100.0 (258) " 100.0 (259) " 100.0 (260) " 100.0 45 (261) " 100.0 (262) " 100.0 (263) » 100.0 (264) " 100.0 50

55

74 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxic ity dient(g/10are) lings (%) (265) 300 100.0 (266) " 100.0 (267) « 100.0 (268) " 100.0 10 (269) " 100.0 (270) " 100.0 - ' (271) " 100.0 (272) " 100.0 (273) " 100.0 15 (274) " 100.0 - (275) " 100.0 — (276) " 100.0 - (277) " 100.0 - 20 (278) " 100.0 (279) " 100.0 - (280) " 100.0 - (281) " 100.0 25 (282) n 100.0 - (283) " 100.0 - (284) " 100.0 - (285) " 100.0 " 30 (286) 100.0 (287) " 100.0 - (288) " 100.0 (289) " 100.0 (290) " 100.0 35 (291) " 100.0 - (292) " 100.0 (293) " 100.0 (294) " 100.0 - 40 (295) " 100.0 - (296) M 100.0 (297) " 100.0 (298) " 100.0 45 (299) " 100.0 (300) M 100.0 (301) " 100.0 (302) " 100.0 50

55

75 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%) (303) 300 100.0 - (304) « 100.0 - (305) " ioo.O (306) » ioo.O 10 (307) « ioo.O (308) - ioo.O (309) - ioo.O (310) - ioo.O " 75 (311) 100.0 (312) - 100.0 (313) " 100.0 (314) " 100.0 (315) " 100.0 20 (316) " 100.0 (317) - 100.0 - (318) - 100.0 - (319) - 100.0 25 (320) " 100.0 (321) " 100.0 (322) " 100.0 (323) " 100.0 - 30 (324) » ioo.O - (325) " 100.0 (326) " 100.0 (327) » 100.0 (328) " 100.0 35 (329) » 100.0 (330) » 100.0 (331) » 100.0 (332) ■• 100.0 40 (333) •• 100.0 (334) « 100.0 (335) » 100.0 (336) » 100.0 45 (337) ■• 100.0 (338) " 100.0 (339) " 100.0 (340) " 100.0 - 50

55

76 EP 0 128 006 B1

Test Dosage rate of Percentage of Phy to- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%) (341) 300 100.0 (342) " ioo.O (343) - ioo.O (344) - 100.0 (345) •' 10 100.0 (346) " ioo.O (347) " 100.0 (348) " 100.0 (349) " 100.0 75 (350) " 100.0 (351) " 100.0 (352) " 100.0 (353) - 100.0 20 (354) " 100.0 (355) " ioo.O (356) » 100.0 (357) " 100.0 " 25 (358) 100.0 (359) " 100.0 (360) " 100.0 (361) " 100.0 (362) " 100.0 30 (363) " 100.0 (364) " 100.0 - (365) » 100.0 (366) " 100.0 35 (367) ■• 100.0 (368) " ioo.O (369) " ioo.O (370) " 100.0 40 (371) " 100.0 (372) " 100.0 (373) " 100.0 (374) " 100.0 45

50

55

77 EP 0 128 006 B1

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings (%}

B 15.0(^/10 a) 73.3

Inoculated and 6 ~ untreated plot 10 Uninoculated and untreated — 100.0 — plot

75

Test example 3 Controlling effect against fusarium wilt of cucumber (Fusarium oxysporum f.sp. cucumerinum)

20 A plastic pot was filled with field soil and then with a uniform mixture of infested soil containing cultured Fusarium oxysporum f.sp. cucumerinum and a prescribed amount of each test compound in the form of dust prepared according to Formulation example 1 until the upper surface of the soil reached a level of 5 cm. In this test, as to hydroxyisoxazole, its prescribed amount was diluted with water and applied to drench the pot filled with the field soil. The seed of cucumber (variety, Shimoshirazuchibai) was sowed at a rate of 25 10/pot and covered with soil. After three weeks' cultivation in a greenhouse, the controlling effect was examined. The results are shown in Table 9.

30 Table 9

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) 35 lings (%) (2) 300 100.0 (4) " 100.0 (5) " 100.0 40 (61) " 100.0 (123) » 100.0 (217) » 100.0 « 45 (221) 100.0 (280) " 100.0 (349) " 100.0 (353) " 100.0 50 C 600 53.3

Inoculated and untreated plot 3<3 ~~

55 Uninoculated and ~ untreated plot 100.0

78 EP 0 128 006 B1

Test example 4 Controlling effect against fusarium wilt of tomato (Fusarium oxysporum f.sp. lycopersici)

Each test compound in the form of emulsifiable concentrate formulated according to Formulation example 4 was diluted with water to a prescribed concentration and sprayed on tomato seedlings (variety, Fukuju No.2) in the three-leaf stage cultivated in a plastic pot so that the spray liquor was thoroughly attached to the leaf surface. After spraying, the seedlings were inoculated by drenching their root with the spore suspension of Fusarium oxysporum f.sp. lycopersici. After inoculation, the seedlings were cultivated for three weeks in a greenhouse, and the controlling effect was examined. The results are shown in Table 10. 10 Table 10

Test Dosage rate of Percentage of phyto- 75 compound active ingre- healthy seed- toxicity dient(g/10are) lings (%)

(2) 1000 100.0 (4) " ioo.O 20 (5) " 100.0 (52) » • 100.0 (61) M 100.0 (91) " 100.0 25 (123) « 100.0 (217) « ioo.O (221) " 100.0 30 (280) " 100.0 (349) " 100.0 - (353) » 100.0 (367) « ioo.O 35 A " 53.3

Inoculated and untreated plot 13.3 — 40 Uninoculated and untreated plot 100.0

45 Test example 5 Controlling effect against verticillium wilt of eggplant (Verticillium albo-atrum)

Soil in a plot (2 m2) was inoculated with 100 g of a wheat bran medium containing cultured Verticillium albo-atrum, and then mixed with a prescribed amount of each test compound in the form of fine granule 50 formulated according to Formulation example 5. In this test, chloropicrin was used as follows : After inoculation with the pathogen, a prescribed amount of chloropicrin was injected into the soil which was then covered with a polyvinyl chloride film and allowed to stand for one week; thereafter, the film was removed, the soil was ploughed and gas release was carried out for further one week. Thereafter, an eggplant seedling (variety, Senryo No.2) in the two-leaf stage was transplanted at a rate of 16/plot and cultivated for 55 about six seeks in a greenhouse, and the controlling effect was examined. The results are shown in Table 1 1 .

79 EP 0 128 006 B1

Table 11

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient (g/lOare) lings (%)

(2) 1000 93.8 - (4) " 97.9 10 (5) " 93.8 (60) " 95.8 (61) " 91.7 (123) " 92.1 75 (289) " 96.6 - (217) " 92.1 (221) " 94.3 " 20 (349) 90.8 - B 30.0 (1/10 a) 54.2

Inoculated and , 0 . untreated plot 25 Uninoculated and ,Q0 Q untreated plot

30

Test example 6 Controlling effect against club-root of Chinese cabbage (Plasmodiophora brassicae)

A plastic pot was filled with field soil and then with a uniform mixture of a soil infested with 35 Plasmodiophora brassicae and a prescribed amount of each test compound in the form of dust formulated according to Formulation example 1 until the upper surface of the soil reached a level of 5 cm. Thereafter, the seed of Chinese cabbage (variety, Taibyo-60 nichi) was sowed at a rate of 15/pot and covered with soil. After four weeks' cultivation in a greenhouse, the controlling effect was examined. The results are shown in Table 12. 40

45

50

55

80 EP 0 128 006 B1

Table 12

Test Dosage rate of Percentage of Phyto- compound active ingre- healthy seed- toxicity dient(g/10are) lings(%)

(2) 1000 93.8 (4) " 93.8 10 (5) " 83.3 (52) " 85.4 (61) " 89.6 " 75 (91) 92.1 (123) " 81.6 (217) " 83.9 (219) " 87.5 20 (220) " 91.3 (221) " 89.7 (279) » 81.2 (349) » 85.2 25 (353) " 90.4

D 2000 72.9 -

Inoculated and - 30 8'9 untreated plot ~

Uninoculated and 100. untreated plot 0

35

Test example 7 Controlling effect against fusarium wilt of cotton (Fusarium oxysporum f.sp. vasinfectum)

40 A plastic pot was filled with field soil and infested soil containing cultured Fusarium oxysporum f.sp. vasinfectum, and the seed of cotton (variety, Coker) dressed with a prescribed amount of each test compound in the form of wettable powder formulated according to Formulation example 3 was sowed at a rate of 10/pot and covered with soil. After three weeks' cultivation in a greenhouse, the controlling effect was examined. 45 The results are shown in Table 13.

50

55

81 EP 0 128 006 B1

Table 13

Test Amount of active Percentage of Phyto- compound ingredient^--^^' healthy seed- toxicity, ^^-^eight lings (1) of dry seed (g/kg)

(91) 4 100.0 10 (217) " 100.0 (219) " 100.0 - (221) " 100.0 75 (247) " 100.0 —

Inoculated and _ g 7 _ untreated plot

20 Uninoculated and _ 10Q Q _ untreated plot

25 Claims

1. A soil disease controlling agent characterized by containing as an active ingredient a 2-cycloal- kenylamine derivative represented by the formula,

30

/

35

wherein R1 represents a hydrogen atom, a hydroxy, amino, lower cycloalkyl, lower cycloalkenyl, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, arylcarbonyloxy or aryl group, a lower alkyl group 40 which may be substituted with a halogen atom or a cyano, nitro, hydroxy, lower alkoxy, lower cycloalkyl, aryl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkyl- carbonyl or dialkylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, R2 represents a hydrogen atom, a hydroxy, amino, lower cycloalkyl, lower cycloalkenyl, lower alkynyl, tetrahydrofurfuryl, 45 piperidyl, arylthio, arylcarbonyloxy or aryl group, a lower alkyl group which may be substituted with a halogen atom or a cyano, nitro, hydroxy, lower alkoxy, lower cycloalkyl, aryl, carboxy, lower alkoxycar- bonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, a lower alkoxy group which may be substituted with an aryl group, or a group represented by the formula, 50

-C - R^ !

55 wherein R3 represents a hydrogen atom, a lower alkynyl, cycloalkyl, cycloalkenyl, aryl, lower alkyl- substituted oxathiinyl, uracilyl, arylcarbonyl or benzdioxanyl group, an alkyl group which may be substituted with a halogen atom or a lower alkoxy, cycloalkoxy, aryl, aryloxy, arylthio, cyano, carboxy or

82 EP 0 128 006 B1

lower alkoxycarbonyl group, or a lower alkenyl group which may be substituted with a halogen atom or a carboxy, lower alkoxy or alkoxycarbonyl group, and X represents an oxygen or sulfur atom or an imino group, or R3 and R1, taken together, may form a lower alkylene or o-phenylene group, or R1 and R2, taken together, may form an alkylene or alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group, an imino group or at least one of substituents, a group represented by the formula,

10 -c - z - c II U X Y

wherein X and Y, which may be the same or different, represent an oxygen or sulfur atom or an 15 imino group, and Z represents a cycloalkylene, cycloalkenylene, bicycloalkylene or arylene group, a lower alkylene group which may be substituted with a hydroxy, lower alkoxy, aryl, lower alkylcar- bonyloxy, methylene, alkylidene, mercapto, arylcarbamoyloxy which may be substituted, or lower alkylcarbonylthio group, a lower alkenylene group which may be substituted with a halogen atom or a carboxy or aryl group, or a substituent represented by the formula -A-R-(in which A represents an 20 oxygen or sulfur atom or an imino group, and R represents a lower alkylene group), or a substituted alkylidene group represented by the formula,

.h* 25

R5

30 wherein R4 and R5, which may be the same or different, represent a hydrogen atom, a nitro, lower cycloalkyl, aryl, dihydropyranyl, carboxy or acyl group, a lower alkyl group which may be substituted with a halogen atom or a hydroxy, lower alkoxy, aryloxy, lower alkoxycarbonyl, di-lower alkylamino, acyl or aryl group, a lower alkenyl group which may be substituted with a halogen atom or a hydroxyl or aryl group, or a lower alkynyl group which may be substituted with an aryl group, or R4 and R5, taken 35 together, may form an alkylene or alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group or an imino group, and n represents 1 , 2, 3 or 4, or its salt, and an inert carrier.

2. A 2-cycloalkenylamine derivative represented by the formula: 40

45 u n

wherein R2 represents amino, C3 alkynyl, C2-3 alkoxycarbonyl-substituted phenylthio, phenylthio or 50 phenylcarbonyloxy group, a C1-5 alkyl group which is substituted with a halogen atom or a cyano, C1-2 alkoxy, C2-3 alkoxycarbonyl, or acetyl group, or a C1-2 alkoxy group which may be substituted with a phenyl group, and n represents 2 or 3.

3. A 2-cycloalkenylamine derivative represented by the formula, 55

83 EP 0 128 006 B1

k"a}y

10 wherein R3 represents a hydrogen atom, Cs cycloalkenyl, benzoyl, benzodioxanyl, thienyl, pyridyl, quinoxalyl, 3-methylbenzofuryl, naphthyl group or

75

20 a Ci-13 alkyl group which may be substituted with a halogen atom, carboxy, phenyl, 3,4-ethylenediox- yphenyl, halogen-substituted phenyl, imidazolyl, triazolyl group, C1-4. alkoxy, halogen-substituted phenoxy, methyl-substituted phenyl, cyano, C2-3 alkoxycarbonyl, phenylthio or C3-10 cycloalkoxy group, a phenyl group which may be substituted with a halogen atom, hydroxy, nitro, carboxyl, C1-2 alkoxy, phenoxy, C1-4. alkyl, cyano, C2-4 dialkylamino or C1 haloalkyl group, a C2-3 alkenyl group 25 which may be substituted with a halogen atom, carboxy, C2-4 alkoxycarbonyl,

30

or C1-2 alkoxy group, a C3-6 cycloalkyl group which may be substituted with carboxy, methyl, dichlorovinyl or phenyl group, a furyl group which may be substituted with a methyl group, a pyrolyl group which may be substituted with a methyl group, X represents an oxygen or sulfur atom, and n 35 represents 2 or 3, provided that the following combinations of n and R3 are excluded:

n = 2 and R3 = methyl, propyl, phenyl, chloromethyl, trichloromethyl, tert-butyl or trifluoromethyl; n = 3 and R3 = methyl or trifluoromethyl group.

40 4. A 2-cycloalkenylamine derivative represented by the formula,

45

50 wherein X and Y, which may be the same or different, represent an oxygen or sulfur atom, Z represents a C3-6 cycloalkylene, cg cycloalkenylene, C6-7 bicycloalkylene pyridylene group, phenylene group which is substituted with a halogen atom or nitro group, C2-3 alkylene group which may be substituted with a hydroxy, C1-2 alkoxy, phenyl, acetoxy, C2-3 alkylidene, mercapto, phenylcarbamoyloxy or 55 acetylthio group, a C2 alkenylene group which may be substituted with a halogen atom or phenyl group, or a substituent represented by the formula -A-R-(in which A represents an oxygen or sulfur atom or an imino group, and R represents a C1 -3 alkylene group), and n represents 2 or 3.

84 EP 0 128 006 B1

5. A 2-cycloalkenylamine derivative represented by the formula,

tCVn

10 wherein R* and R5, which may be the same or different, represent a hydrogen atom, a nitro, lower cycloalkyl, aryl, dihydropyranyl, carboxy or acyl group, a lower alkyl group which may be substituted with a halogen atom or a hydroxy, lower alkoxy, aryloxy, lower alkoxycarbonyl, di-lower alkylamino, acyl or aryl group, a lower alkenyl group which may be substituted with a halogen atom or a hydroxyl or aryl 15 group, or a lower alkynyl group which may be substituted with an aryl group, or R* and R5, taken together, may form an alkylene or alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group or an imino group, and n represents 1 , 2, 3 or 4, provided that the following cases are excluded: when n is 1, R* is a butyl group and R5 is a hexyl group, or R+ and R5, taken together.form a 2,4,4-trimethyl-1-pentenylene group; and when n is 2, R* and R5, taken together, form a pentylene 20 group.

6. A method for producing a 2-cycloalkenylamine derivative represented by the formula,

25

(CH,) 2 n V

30

wherein R5 represents a hydrogen atom, amino, lower alkynyl tetrahydrofurfuryl, piperidyl, arylthio or arylcarbonyloxy group, a lower alkyl group which is substituted with a halogen atom or a cyano, nitro, lower alkoxyl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower 35 alkylcarbonyl or dialkylamino group, a lower alkenyl group which is substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, Rs represents a lower alkynyl, tetrahydrofurfuryl, piperidyl, arylcarbonyloxy or arylthio group, a lower alkyl group which is substituted with a halogen atom or a cyano, nitro, lower alkoxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, lower alkylcarbonyl, dialkylamino or aryloxycarbonyl group, a lower alkenyl group 40 which is substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, and n represents 1, 2, 3 or 4, characterized in that a compound represented by the formula,

45

50

wherein RG and n represent the same meanings as above, is reacted with a compound represented by the formula,

55 L - Rs

wherein R8 represents the same meaning as above and L represents a halogen atom, an arylcarbonyloxy, hydroxy or lower alkylsulfonyloxy group, or a benzenesulfonyloxy group which may be

85 EP 0 128 006 B1

substituted with a lower alkyl group.

7. A method for producing a 2-cycIoalkenylamine derivative represented by the formula,

5

w

wherein R6 and R7, which may be the same or different, represent a hydrogen atom, amino, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio or arylcarbonyloxy group, a lower alkyl group which is 75 substituted with a halogen atom or a cyano, nitro, lower alkoxy, lower alkoxycarbonyl, lower alkenylox- ycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which is substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, or Rs and R7, taken together, may form an alkenylene group which may contain an oxygen or sulfur atom, a carbonyl group, an imino group or at least one of substituents, and n 20 represents 1 , 2, 3 or 4, provided that a case wherein R6 and R7 are a hydrogen atom at the same time is excluded, characterized in that a compound represented by the formula,

R6 25 H-N< 7

wherein Rs and R7 represent the same meanings as above, is reacted with a compound 30 represented by the formula,

35 (CH2>n

40 wherein E represents a halogen atom, a lower alkylsulfonyloxy group or a benzenesulfonyloxy group which may be substituted with a lower alkyl group, and n represents the same meaning as above.

8. A method for producing a 2-cycloalkenylamine derivative represented by the formula, 45

n>r 50 'cyn/

wherein R1 represents a hydrogen atom, amino, lower cycloalkyl, lower cycloalkenyl, lower alkynyl, 55 tetrahydrofurfuryl, piperidyl, arylthio, or arylcarbonyloxy group, a lower alkyl group which may be substituted with a halogen atom or a cyano, nitro, hydroxy, lower alkoxy, lower cycloalkyl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, or a lower

86 EP 0 128 006 B1

alkoxy group which may be substituted with an aryl group, R3 represents a hydrogen atom, a lower alkynyl, cycloalkyl, cycloalkenyl.aryl, lower alkyl-substituted oxathiinyl, uracilyl, arylcarbonyl or benz- dioxanyl group, an alkyl group which may be substituted with a halogen atom or a lower alkoxy, cycloalkoxy, aryl, aryloxy, arylthio, cyano, carboxy or lower alkoxycarbonyl group, or a lower alkenyl 5 group which is substituted with a carboxy, lower alkoxy group, X represents an oxygen or sulfur atom or an imino group, and n represents 2, 3 or 4, provided that when X is an oxygen atom and R1 is a hydrogen atom, the following combinations of n and R3 are excluded: n = 2 and R3 = methyl, propyl, phenyl, chloromethyl, trichloromethyl, tert-butyl or trifluoromethyl; n = 3 and R3 = methyl or trifluoromethyl; and n = 4 and R3 = methyl, when X is an imino group, R1 is a hydrogen atom and n is 2, 10 R3 is not a trichloromethyl group, characterized in that a compound represented by the formula,

S\ is \ Vnhr1 /

20 wherein R1 and n represent the same meanings as above, is reacted with a compound represented by the formula,

M - C - R3 25 II X

wherein R3 and X represent the same meanings as above, and M represents a halogen atom, a 30 hydroxy, lower atkoxy, mercapto or lower alkylthio group, or a group represented by the formula

-0-C-R3 U x

(in which R3 and X represent the same meanings as above).

9. A method for producing a 2-cycloalkenylamine derivative represented by the formula, 40

45

wherein R3 represents a hydrogen atom, a hydroxy, lower cycloalkyl, lower cycloalkenyl, lower 50 alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, arylcarbonyloxy or aryl group, a lower alkyl group which may be substituted with a halogen atom or a cyano, hydroxy, lower alkoxy, lower cycloalkyl, aryi, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dial- kylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, Z' represents a cycloalkenylene, 55 cycloalkylene, bicycloalkylene or arylene group, a lower alkylene group which may be substituted with a hydroxy, lower alkoxy, aryl, lower alkylcarbonyloxy, methylene, alkylidene, mercapto, carbamoyloxy group which may be substituted, or lower alkylcarbonylthio group, or a lower alkenylene group which may be substituted with a halogen atom or a carboxy or aryl group, and n represents 2, 3 or 4,

87 EP 0 128 006 B1

characterized in that a compound represented by the formula,

w wherein R9 and n represent the same meanings as above, is reacted with a compound represented by the formula,

O 75 n

0 20 wherein Z' represents the same meaning as above.

10. A method for producing a 2-cycloalkenylamine derivative represented by the formula,

25

30

wherein R3 represents a hydrogen atom, a lower alkynyl, cycloalkyl.cycloalkenyl, aryl, lower alkyl- substituted oxathiinyl, uracilyl, arylcarbonyl or benzdioxanyl group, an alkyl group which may be 35 substituted with a halogen atom or a lower alkoxy, cycloalkoxy, aryl, aryloxy, arylthio, cyano, carboxy or lower alkoxycarbonyl group, or a lower alkenyl group which is substituted with a halogen atom or a carboxy, lower alkoxy group, X represents an oxygen or sulfur atom or an imino group, R10 represents a lower cycloalkyl, lower cycloalkenyl, arylthio, lower alkynyl, tetrahydrofurfuryl, piperidyl, or arylcar- bonyloxy group, a lower alkyl group which may be substituted with a halogen atom or a cyano.hydroxy, 40 lower cycloalkyl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, or a lower alkenyl group which may be substituted with a halogen atom or an aryl group, and n represents 2, 3 or 4, characterized in that a compound represented by the formula,

45

3 "f 50

wherein R3, X and n represent the same meanings as above, is reacted with a compound represented by the formula, 55 R10 - Lf

wherein L' represents a halogen atom, an arylcarbonyloxy or lower alkylsulfonyloxy group, or a

88 EP 0 128 006 B1

benzenesulfonyloxy group which may be substituted with a lower alkyl group, and R10 represents the same meaning as above.

11. A method for producing a 2-cycloalkenylamine derivative represented by the formula, 5

w

75 wherein R1 represents a hydrogen atom, amino, lower cycloalkyl, lower cycloalkenyl, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, or arylcarbonyloxy group, a lower alkyl group which may be substituted with a halogen atom or a cyano, nitro, hydroxy, lower alkoxy, lower cycloalkyl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, or a lower 20 alkoxy group which may be substituted with an aryl group, R3 represents a hydrogen atom, a lower alkynyl, cycloalkyl, cycloalkenyl, aryl, lower alkyl-substituted oxathiinyl, uracilyl, arylcarbonyl or benz- dioxanyl group, an alkyl group which may be substituted with a halogen atom or a lower alkoxy, cycloalkoxy, aryl, aryloxy, arylthio, cyano, carboxy or lower alkoxycarbonyl group, or a lower alkenyl group which is substituted with a carboxy, lower alkoxy group, X represents an oxygen or sulfur atom 25 or an imino group, or R3 and R1, taken together, may form a lower alkylene or o-phenylene group, and n represents 2, 3 or 4, provided that when X is an oxygen atom and R1 is a hydrogen atom, the following combinations of n and R3 are excluded: n = 2 and R3 = methyl, propyl, phenyl, chloromethyl, trichloromethyl, tert-butyl or trifluoromethyl; n = 3 and R3 = methyl or trifluoromethyl; and n = 4 and R3 = methyl, when X is an imino group, R1 is a hydrogen atom and n is 2, R3 is not a trichloromethyl 30 group, characterized in that a compound represented by the formula,

R1

35 H - N CR3 II X

40 wherein R1, R3 and X represent the same meanings as above, is reacted with a compound represented by the formula,

45

(CH.)_ V2 n

50

wherein E represents a halogen atom, a lower alkylsulfonyloxy group or a benzenesulfonyloxy group which may be substituted with a lower alkyl group, and n represents the same meaning as above. 55 12. A method for producing a 2-cycloalkenylamine derivative represented by the formula,

89 EP 0 128 006 B1

wherein R1 represents a hydrogen atom, a hydroxy, amino, lower cycloalkyl, lower cycloalkenyl, w lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio, arylcarbonyloxy or aryl group, a lower alkyl group which may be substituted with a halogen atom or a cyano, nitro, hydroxy, lower alkoxy, lower cycloalkyl, aryl, carboxy, lower alkoxycarbonyl, lower alkenyloxycarbonyl, aryloxycarbonyl, lower alkyl- carbonyl or dialkylamino group, a lower alkenyl group which may be substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, R3 represents a 75 hydrogen atom, a lower alkynyl, cycloalkyl, cycloalkenyl, aryl, lower alkyl-substituted oxathiinyl, uracilyl, arylcarbonyl or benzdioxanyl group, an alkyl group which may be substituted with a halogen atom or a lower alkoxy, cycloalkoxy, aryl, aryloxy, arylthio, cyano, carboxy or lower alkoxycarbonyl group, or a lower alkenyl group which may be substituted with a halogen atom or a carboxy, lower alkoxy or alkoxycarbonyl group, and n represents 2, 3, or 4, characterized in that a compound represented by the 20 formula,

25

30 wherein R\ R3 and n represent the same meanings as above, is reacted with phosphorus pentasulfide.

13. A method for producing a 2-cycloalkenylamine derivative represented by the formula,

35 -£*

(CH.J

40

wherein X and Y, which may be the same or different, represent an oxygen or sulfur atom or an imino group, and Z represents a cycloalkylene, bicyloalkylene or arylene group, a lower alkylene group which may be substituted with a hydroxy, lower alkoxy, aryl, lower alkylcarbonyloxy, methylene, 45 alkylidene, mercapto, arylcarbamoyloxy which may be substituted, or lower alkylcarbonylthio group, a lower alkenylene group which may be substituted with a halogen atom or a carboxy or aryl group, or a substituent represented by the formula -A-R- (in which A represents an oxygen or sulfur atom and R represents a lower alkylene group), and n represents 2, 3 or 4, provided that a case wherein when n is 2 or 3 and X and Y are an oxygen atom, Z is an o-phenylene group is excluded, characterized in that so 2-cycloalkenylamine represented by the formula,

55 (CH,J

90 EP 0 128 006 B1

wherein n represents the same meaning as above, is reacted with a compound represented by the formula,

X

Z HO-*/ Y •

wherein X, Y and Z represent the same meaning as above, or its anhydride.

14. A method for producing a 2-cycloalkenylamine derivative represented by the formula, 75

20

25 wherein X and Y, which may be the same or different, represent an oxygen or sulfur atom or an imino group, and Z represents a cycloalkylene, bicycloalkylene or arylene group, a lower alkylene group which may be substituted with a hydroxy, lower alkoxy, aryl, lower alkylcarbonyloxy, methylene, alkylidene, mercapto, arylcarbamoyloxy which may be substituted, or lower alkylcarbonylthio group, a lower alkenylene group which may be substituted with a halogen atom or a carboxy or aryl group, or a 30 substituent represented by the formula -A-R-(in which A represents an oxygen or sulfur atom, and R represents a lower alkylene group), and n represents 2, 3 or 4, provided that a case wherein when n is 2 or 3 and X and Y are an oxygen atom, Z is an o-phenylene group is excluded, characterized in that a compound represented by the formula,

35

40

wherein E represents a halogen atom, a lower aikylsulfonyloxy group or a benzenesulfonyloxy group which may be substituted with a lower alkyl group, and n represents the same meaning as 45 above, is reacted with a compound represented by the formula,

X

so HN Z

Y

55 wherein X, Y and Z represent the same meanings as above,

15. A method for producing a 2-cycloalkenylamine derivative represented by the formula,

91 EP 0 128 006 B1

(CVn

10 wherein X represents an oxygen or sulfur atom or an imino group, Z represents a cycloalkylene, cycloalkenylene, bicycloalkylene or arylene group, a lower alkylene group which may be substituted with a hydroxy, lower alkoxy, aryl, lower alkylcarbonyloxy, methylene, alkylidene, mercapto, arylcar- bamoyloxy which may be substituted, or lower alkylcarbonylthio group, a lower alkenylene group which may be substituted with a halogen atom or a carboxy or aryl group, or a substituent represented by the 75 formula -A-R-(in which A represents an oxygen or sulfur atom and R represents a lower alkylene group), and n represents 2, 3 or 4, characterized in that a compound represented by the formula,

20

{Ch]n

25

wherein X, Z and n represent the same meanings as above, is reacted with phosphorus pentasul- fide.

30 16. A method for producing a 2-cycloalkenylamine derivative represented by the formula,

35 (C«2»n

wherein R* and R5, which may be the same or different, represent a hydrogen atom, a nitro, lower 40 cycloalkyl, aryl, dihydropyranyl, carboxy or acyl group, a lower alkyl group which may be substituted with a halogen atom or a hydroxy, lower alkoxy, aryloxy, lower alkoxycarbonyl, di-lower alkylamino, acyl or aryl group, a lower alkenyl group which may be substituted with a halogen atom or a hydroxy or aryl group, or a lower alkynyl group which may be substituted with an aryl group, or R4 and R5, taken together, may form an oxygen or sulfur atom, a carbonyl group or an alkylene or alkenylene group 45 which may contain an imino group, and n represents 1 , 2, 3 or 4, provided that the following cases are excluded: when n is 1, R+ is a butyl group and R5 is a hexyl group, or R* and R5, taken together, form a 2,4,4-trimethyl-1-pentenylenegroup; and when n is 2, R* and R5, taken together, form a pentylene group, characterized in that 2-cycloalkenylamine represented by the formula,

50

55

wherein n represents the same meaning as above, is reacted with a carbonyl compound represented

92 EP 0 128 006 B1

by the formula,

5 / 0 = Cv V to wherein R+ and R5 represent the same meanings as above.

17. A method for producing the salt of a 2-cycloalkenylamine derivative characterized in that a compound represented by the formula,

75

(CVn 20

wherein RG and R7, which may be the same or different, represent a hydrogen atom, amino, lower alkynyl, tetrahydrofurfuryl, piperidyl, arylthio or arylcarbonyloxy group, a lower alkyl group which is 25 substituted with a halogen atom or a cyano, nitro, lower alkoxy, lower alkoxycarbonyl, lower alkenylox- ycarbonyl, aryloxycarbonyl, lower alkylcarbonyl or dialkylamino group, a lower alkenyl group which is substituted with a halogen atom or an aryl group, or a lower alkoxy group which may be substituted with an aryl group, and n represents 1 , 2, 3 or 4, provided that when both R6 and R7 are a hydrogen atom, salts with the following acids are excluded for each value of n: when n is 1, hydrochloric acid, 30 picric acid; when n is 2, hydrochloric acid, hydrobromic acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, (2-cyclohexenylamino)methanesulfonic acid, (3- cyclohexenylamino)methanesulfonic acid, acetic acid, lactic acid, succinic acid, fumaric acid, maleic acid, malic acid, tartaric acid, citric acid, ascorbic acid, benzoic acid, salicylic acid, phenylacetic acid, mandelic acid, 4,4'-methylenebis (3-hydroxy-/3-naphthoic acid); when n is 3, hydrochloric acid; and 35 when n is 4, picric acid, is reacted with an inorganic, organic or Lewis acid.

Revendications

1. Agent pour combattre des maladies de plantes dans le sol, caracterise en ce qu'il contient comme 40 ingredient actif un derive de 2-cycloalcenylamine represente par la formule

45

so dans laquelle R1 represente un atome d'hydrogene, un groupe hydroxy, amino, cycloalkyle inferieur, cycloalcenyle inferieur, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio, arylcarbony- loxy ou aryle, un groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un substituant cyano, nitro, hydroxy, alkoxy inferieur, cycloalkyle inferieur, aryle, carboxy, (alkoxy infe- rieur)carbonyle, (alcenyloxy inferieur) carbonyle, aryloxycarbonyle, (alkyle inferieur)carbonyle ou dialky- 55 lamino, un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe aryle, ou un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, R2 represente un atome d'hydrogene, un groupe hydroxy, amino, cycloalkyle inferieur, cycloalcenyle inferieur, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio, arylcarbonyloxy ou aryle, un groupe alkyle inferieur qui

93 EP 0 128 006 B1

peut etre substitue avec un atome d'halogene ou un groupe cyano, nitro, hydroxy, alkoxy inferieur, cycloalkyle inferieur, aryle, carboxy, (alkoxy inferieur)carbonyle (alcenyloxy inferieur)carbonyle, aryloxy- carbonyle, (alkyle inferieur)carbonyle ou dialkylamino, un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe aryle, un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, ou un groupe represente par la formule

-C - R3 li X w

dans laquelle Ft3 represente un atome d'hydrogene, un groupe alcynyle inferieur, cycloalkyle, cycloalcenyle, aryle, oxathiinyle a substituant alkyle inferieur, uracilyle, arylcarbonyle ou benzodioxan- nyle, un groupe alkyle qui peut etre substitue avec un atome d'halogene ou un groupe alkoxy inferieur, 75 cycloalkoxy, aryle, aryloxy, arylthio, cyano, carboxy ou (alkoxy inferieur)carbonyle ou un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe carboxy, alkoxy inferieur ou alkoxycarbonyle, et X represente un atome d'oxygene ou de soufre ou un groupe imino, ou bien R3 et R1, considered ensemble, peuvent former un groupe alkylene inferieur ou o-phenylene, ou bien R1 et R2, considered ensemble, peuvent former un groupe alkylene ou alcenylene qui peut 20 contenir un atome d'oxygene ou de soufre, un groupe carbonyle, un groupe imino ou au moins un de plusieurs substituants, un groupe represente par la formule

-c - z - c- 1 I X Y

dans laquelle X et Y, qui peuvent etre identiques ou differents, represented un atome d'oxygene 30 ou de soufre ou un groupe imino et Z represente un groupe cycloalkylene, cycloalcenylene, cycloalky- lene ou arylene, un groupe alkylene inferieur qui peut etre substitue avec un radical hydroxy, alkoxy inferieur, aryle, (alkyle inferieur)carbonyloxy, methylene, alkylidene, mercapto, arylcarbamoyloxy qui peut etre substitue, ou un groupe (alkyle inferieur)carbonylthio, un groupe alcenylene inferieur qui peut etre substitue avec un atome d'halogene ou un groupe carboxy ou aryle, ou un substituant represente 35 par la formule -A-R- (dans laquelle A represente un atome d'oxygene ou de soufre ou un groupe imino et R represente un groupe alkylene inferieur), ou un groupe alkylidene substitue represente par la formule

40

45

dans laquelle R+ et R5, qui peuvent etre identiques ou differents, represented un atome d'hydroge- ne, un groupe nitro, cycloalkyle inferieur, aryle, dihydropyrannyle, carboxy ou acyle, un groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe hydroxy, alkoxy inferieur, 50 aryloxy, (alkoxy inferieur)carbonyle, di(alkyle inferieur)amino, acyle ou aryle, un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou avec un groupe hydroxy ou aryle, ou un groupe alcynyle inferieur qui peut etre substitue avec un groupe aryle, ou bien R* et R5, considered ensemble, peuvent former un groupe alkylene ou alcenylene qui peut contenir un atome d'oxygene ou de soufre, un groupe carbonyle ou un groupe imino, 55 et n a la valeur 1 , 2, 3 ou 4, ou un sel de ce derive, et un support inerte.

2. Derive de 2-cycloalcenylamine represente par la formule

94 EP 0 128 006 B1

lCVn

dans laquelle R2 represente un groupe amino, alcynyle en C3, phenylthio a substituant alkoxycarbonyle w en C2 ou C3, un groupe phenylthio ou phenylcarbonyloxy, un groupe alkyle en Ci a C5 qui est substitue avec un atome d'halogene ou un groupe cyano, alkoxy en Ci ou C2, alkoxycarbonyle en C2 ou C3 ou acetyle, ou un groupe alkoxy en Ci ou C2 qui peut etre substitue avec un groupe phenyle, et n a la valeur 2 ou 3.

75 3. Derive de 2-cycloalcenylamine represente par la formule

h r \ , (CHO. /"v/* vy

25 dans laquelle R3 represente un atome d'hydrogene, un groupe cycloalcenyle en C6, benzoyle, benzodioxannyle, thienyle, pyridyle, quinoxalyle, 3-methylbenzofuryle, naphtyle ou un groupe

30

35 un groupe alkyle en Ci a Ci 3 qui peut etre substitue avec un atome d'halogene, un groupe carboxy, phenyle, 3,4-ethylenedioxyphenyle, phenyle a substituant halogeno, imidazolyle, triazolyle, un groupe alkoxy en Ci a C+, phenoxy a substituant halogeno, phenyle a substituant methyle, cyano, alkoxycar- bonyle en C2 ou C3, phenylthio ou cycloalkoxy en C3 a C10, un groupe phenyle qui peut etre substitue avec un atome d'halogene, un groupe hydroxy, nitro, carboxyle, alkoxy en Ci ou C2, phenoxy, alkyle 40 en Ci a C4., cyano, dialkylamino en C2 a C+ ou un groupe halogenalkyle en Ci, un groupe alcenyle en C2 ou C3 qui peut etre substitue avec un atome d'halogene, un groupe carboxy, alkoxycarbonyle en C2 aCt,

45 tO

ou un groupe alkoxy en Ci ou C2, un groupe cycloalkyle en C3 a C6 qui peut etre substitue avec un 50 groupe carboxy, methyle, dichlorovinyle ou phenyle, un groupe furyle qui peut etre substitue avec un groupe methyle, un groupe pyrrolyle qui peut etre substitue avec un groupe methyle, X represente un atome d'oxygene ou de soufre et n a la valeur 2 ou 3, sous reserve que les associations suivantes entre n et R3 sont exclues : n = 2 et R3 = methyle, propyle, phenyle, chloromethyle, trichloromethyle, tertio-butyle, ou trifluoromethy- 55 le ; n = 3 et R3 = methyle ou trifluoromethyle.

4. Derive de 2-cycloalcenylamine represente par la formule

95 EP 0 128 006 B1

dans laquelle X et Y, qui peuvent etre identiques ou differents, representent un atome d'oxygene ou de io soufre, Z represente un groupe cycloalkylene en C3 a Cs, cycloalcenylene en Cs, bicycloalkylene en C6 ou C7, pyridylene, un groupe phenylene qui est substitue avec un atome d'halogene ou un groupe nitro, un groupe alkylene en C2 ou C3 qui peut etre substitue avec un groupe hydroxy, alkoxy en C1 ou C2, phenyle, acetoxy, alkylidene en C2 ou C3, mercapto, phenylcarbamoyloxy ou acetylthio, un groupe alcenylene en C2 qui peut etre substitue avec un atome d'halogene ou un groupe phenyle, ou un 75 substituant represente par la formule -A-R- (dans laquelle A represente un atome d'oxygene ou de soufre ou un groupe imino et R represente un groupe alkylene en C1 a C3) et n a la valeur 2 ou 3.

5. Derive de 2-cycloaicenylamine represente par la formule

20

25

dans laquelle R4 et R5, qui peuvent etre identiques ou differents, representent un atome d'hydroge- ne, un groupe nitro, cycloalkyle inferieur, aryle, dihydropyrannyle, carboxy ou acyle, un groupe alkyle 30 inferieur qui peut etre substitue avec un atome d'halogene ou un groupe hydroxy, alkoxy inferieur, aryloxy, (alkoxy inferieur)carbonyle, di(alkyle inferieur)amino, acyle ou aryle, un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe hydroxy ou aryle, ou un groupe alcynyle inferieur qui peut etre substitue avec un groupe aryle, ou bien R4 et R5, pris ensemble, peuvent former un groupe alkylene ou alcenylene qui peut contenir un atome d'oxygene ou de soufre, 35 un groupe carbonyle ou un groupe imino, et n a la valeur 1 , 2, 3 ou 4 sous reserve que les cas suivants soient exclus : lorsque n est egal a1,R* est un groupe butyle et R5 est un groupe hexyle, ou bien R* et R5, pris ensemble, torment un groupe 2,4,4-trimethyl-1 -pentenylene ; et lorsque n a la valeur 2, R* et R5, pris ensemble, forment un groupe pentylene.

40 6. Procede de production d'un derive de 2-cycIoalcenylamine represente par la formule

45 I (CVn

so dans laquelle R6 represente un atome d'hydrogene, un groupe amino, alcynyle inferieur, tetrahy- drofurfuryle, piperidyle, arylthio ou arylcarbonyloxy, un groupe alkyle inferieur qui est substitue avec un atome d'halogene ou un groupe cyano, nitro, alkoxy inferieur, carboxy, (alkoxy inferieur)carbonyle, (alcenyloxy inferieur)carbonyle, aryloxycarbonyle, (alkyle inferieur)carbonyle ou dialkylamino, un groupe alcenyle inferieur qui est substitue avec un atome d'halogene ou un groupe aryle, ou un groupe alkoxy 55 inferieur qui peut etre substitue avec un groupe aryle, R8 represente un groupe alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylcarbonyloxy ou arylthio, un groupe alkyle inferieur qui est substitue avec un atome d'halogene ou un groupe cyano, nitro, alkoxy inferieur, (alkoxy inferieur)carbonyle, (alcenyloxy inferieur)carbonyle, (alkyle inferieur)carbonyle, dialkylamino ou aryloxycarbonyle, un groupe

96 EP 0 128 006 B1

alcenyle inferieur qui est substitue avec un atome d'halogene ou un groupe aryle, ou un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, et N represente la valeur 1 , 2, 3 ou 4, caracterise en ce qu'un compose represente par la formule

w

dans laquelle RG et n ont les memes definitions que ci-dessus, est amene a reagir avec un compose represente par la formule 15 L- R8

dans laquelle R8 a la meme definition que ci-dessus et L represente un atome d'halogene, un groupe arylcarbonyloxy, hydroxy ou (alkyle inferieur)sulfonyloxy, ou un groupe benzenesulfonyloxy qui 20 peut etre substitue avec un groupe alkyle inferieur.

7. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule

25

30 dans laquelle RG et R7, qui peuvent etre identiques ou differents, represented un atome d'hydroge- ne, un groupe amino, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio ou arylcarbonyloxy, un groupe alkyle inferieur qui est substitue avec un atome d'halogene ou un groupe cyano, nitro, alkoxy inferieur, (alkoxy inferieur)carbonyle, (alcenyle inferieur)oxycarbonyle, aryloxycarbonyle (alkyle infe- 35 rieur)carbonyle ou diaikylamino, un groupe alcenyle inferieur qui est substitue avec un atome d'haloge- ne ou un groupe aryle, ou un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, ou bien R6 et R7, pris ensemble, peuvent former un groupe alcenylene qui peut contenir un atome d'oxygene ou de soufre, un groupe carbonyle, un groupe imino ou au moins Tun de plusieurs substituants, et n represente la valeur 1, 2, 3 ou 4, sous reserve que soit exclus le cas ou Rs et R7 40 represented en meme temps un atome d'hydrogene, caracterise en ce qu'un compose represente par la formule

R6 h-n

dans laquelle RG et R7 ont les memes definitions que ci-dessus, est amene a reagir avec un 50 compose represente par la formule

55

97 EP 0 128 006 B1

io dans laquelle E represente un atome d'halogene, un groupe (alkyle inferieur)sulfonyloxy ou un groupe benzenesulfonyloxy qui peut etre substitue avec un groupe alkyle inferieur, et n a la meme definition que ci-dessus.

8. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule 75

(CH )n

25 dans laquelle R1 represente un atome d'hydrogene, un groupe amino, cycloalkyle inferieur, cycloalcenyle inferieur, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio ou arylcarbonyloxy, un groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe cyano, nitro, hydroxy, alkoxy inferieur, cycloalkyle inferieur, carboxy, (alkoxy inferieur)carbonyle, (alcenyle inferieur)- oxycarbonyle, aryloxycarbonyle, (alkyle inferieur)carbonyle ou dialkylamino, un groupe alcenyle infe- 30 rieur qui peut etre substitue avec un atome d'halogene ou un groupe aryle, ou un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, R3 represente un atome d'hydrogene, un groupe alcynyle inferieur, cycloalkyle, cycloalcenyle, aryle, oxathiinyle a substituant alkyle inferieur, uracilyle, arylcarbonyle ou benzodioxannyle, un groupe alkyle qui peut etre substitue avec un atome d'halogene ou un groupe alkoxy inferieur, cycloalkoxy, aryle, aryloxy, arylthio, cyano, carboxy ou (alkoxy inferieur)- 35 carbonyle, ou un groupe alcenyle inferieur qui est substitue avec un groupe carboxy, alkoxy inferieur, X represente un atome d'oxygene ou de soufre ou un groupe imino et n a la valeur 2, 3 ou 4, sous reserve que lorsque X est un atome d'oxygene et R1 est un atome d'hydrogene, les associations suivantes entre n et R3 soient exclues : n = 2 et R3 = methyle, propyle, phenyle, chloromethyle, trichloromethyle, tertio-butyle ou trifluoromethyle ; n = 3 et R3 = methyle ou trif luoromethyle ; et n = 4 et 40 R3 = methyle, lorsque X est un groupe imino, R1 est un atome d'hydrogene et n est egal a 2, R3 n'est pas un groupe trichloromethyle, caracterise en ce qu'un compose represente par la formule

45 c^s-.

/

50 dans laquelle R1 et n ont les memes definitions que ci-dessus, est amene a reagir avec un compose represente par la formule

M - C - R3 I! X

98 EP 0 128 006 B1

dans laquelle R3 et X ont la meme definition que ci-dessus et M represente un atome d'halogene, un groupe hydroxy, alkoxy inferieur, mercapto ou alkylthio inferieur ou un groupe represente par la formule

-O-C-R3 II X 10 dans laquelle R3 et X ont les memes definitions que ci-dessus.

9. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule

75 ^K

20

dans laquelle R9 represente un atome d'hydrogene, un groupe hydroxy, cycloalkyle inferieur, cycloalcenyle inferieur, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio, arylcarbonyloxy ou 25 aryle, un groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe cyano, hydroxy, alkoxy inferieur, cycloalkyle inferieur, aryle, carboxy, (alkoxy inferieur)carbonyle, (alcenyle inferieur)oxycarbonyle, aryloxycarbonyle, (alkyle inferieur)carbonyle ou dialkylamino, un groupe alceny- le inferieur qui peut etre substitue avec un atome d'halogene ou un groupe aryle, ou un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, Z' represente un groupe cycloalcenylene, 30 cycloalkylene, bicycloalkylene ou arylene, un groupe alkylene inferieur qui peut etre substitue avec un groupe hydroxy, alkoxy inferieur, aryle, (alkyle inferieur)carbonyloxy, methylene, alkylidene, mercapto, carbamoyloxy qui peut etre substitue, ou un groupe (alkyle inferieur)carbonylthio, ou un groupe alcenylene inferieur qui peut etre substitue avec un atome d'halogene ou un groupe carboxy ou aryle, et n a la valeur 2, 3 ou 4, caracterise en ce qu'un compose represente par la formule 35

dans laquelle R9 et n ont les memes definitions que ci-dessus, est amene a reagir avec un compose represente par la formule 45

°YZ' 50 II 0

dans laquelle Z' a la meme definition que ci-dessus.

55 10. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule

99 EP 0 128 006 B1

dans laquelle R3 represente un atome d'hydrogene, un groupe alcynyle inferieur, cycloalkyle, io cycloalcenyle, aryle, oxathiinyle a substituant alkyle inferieur, uracilyle, arylcarbonyle ou benzodioxan- nyle, un groupe alkyle qui peut etre substitue avec un atome d'halogene ou un groupe alkoxy inferieur, un groupe cycloalkoxy, aryle, aryloxy, arylthio, cyano, carboxy ou (alkoxy inferieur)carbonyle, ou un groupe alcenyle inferieur qui est substitue avec un atome d'halogene ou un groupe carboxy, alkoxy inferieur, X represente un atome d'oxygene ou de soufre ou un groupe imino, R10 represente un groupe 15 cycloalkyle inferieur, cycloalcenyle inferieur, arylthio, alcynyle inferieur, tetrahydrofurfuryle, piperidyle ou arylcarbonyloxy, un groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe cyano, hydroxy, cycloalkyle inferieur, carboxy, (alkoxy inferieur)carbonyle, (alcenyle inferieur)- oxycarbonyle, aryloxycarbonyle, (alkyle inferieur)carbonyle ou dialkylamino, ou un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe aryle et n a la valeur 2, 3 ou 4, 20 caracterise en ce qu'un compose represente par la formule

25 (CH?>n

dans laquelle R3, X et n ont les memes definitions que ci-dessus, est amene a reagir avec un 30 compose represente par la formule

dans laquelle L' represente un atome d'halogene, un groupe arylcarbonyloxy ou un groupe (alkyle 35 inferieur)sulfonyloxy ou un groupe benzenesulfonyloxy qui peut etre substitue avec un groupe alkyle inferieur et R10 a la meme definition que ci-dessus.

11. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule

40

(CVn 45

dans laquelle R1 represente un atome d'hydrogene, un groupe amino, cycloalkyle inferieur, cycloalcenyle inferieur, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio ou arylcarbonyloxy, un so groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe cyano, nitro, hydroxy, alkoxy inferieur, cycloalkyle inferieur, carboxy, (alkoxy inferieur)carbonyle, (alcenyle inferieur)- oxycarbonyle, aryloxycarbonyle, (alkyle inferieur)carbonyle ou dialkylamino, un groupe alcenyle infe- rieur qui peut etre substitue avec un atome d'halogene ou un groupe aryle, ou un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, R3 represente un atome d'hydrogene, un groupe 55 alcynyle inferieur, cycloalkyle, cycloalcenyle, aryle, oxathiinyle a substituant alkyle inferieur, uracilyle, arylcarbonyle ou benzodioxannyle, un groupe alkyle qui peut etre substitue avec un atome d'halogene ou un groupe alkoxy inferieur, un groupe cycloalkoxy, aryle, aryloxy, arylthio, cyano, carboxy ou (alkoxy inferieur)carbonyle, ou un groupe alcenyle inferieur qui est substitue avec un groupe carboxy, un

100 EP 0 128 006 B1

groupe aikoxy inferieur, X represente un atome d'oxygene ou de soufre ou un groupe imino, ou bien R3 et R1, pris ensemble, peuvent former un groupe alkylene inferieur ou un groupe o-phenylene, et n a la valeur 2, 3 ou 4, sous reserve que lorsque X est un atome d'oxygene et R1 est un atome d'hydrogene, les associations suivantes entre n et R3 soient exclues : n = 2 et R3 est un groupe methyle, propyle, 5 phenyle, chloromethyle, trichloromethyle, tertio-butyle ou trifluoromethyle ; n = 3 et R3 = methyle ou trifluoromethyle ; et n = 4 et R3 = methyle, lorsque X est un groupe imino, R1 est un atome d'hydrogene et n est egal a 2, R3 n'est pas un groupe trichloromethyle, caracterise en ce qu'un compose represente par la formule

1

H - N CR3 II « X

dans laquelle R1, R3 et X ont les memes definitions que ci-dessus, est amene a reagir avec un compose represente par la formule 20

(CH,)_ V2 n 25

dans laquelle E represente un atome d'halogene, un groupe (alkyle inferieur)sulfonyloxy ou benzenesulfonyloxy qui peut etre substitue avec un groupe alkyle inferieur et n a la meme definition 30 que ci-dessus.

12. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule

35

40

dans laquelle R1 represente un atome d'hydrogene, un groupe hydroxy, amino, cycloalkyle inferieur, cycloalcenyle inferieur, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio, arylcarbony- 45 loxy ou aryle, un groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe cyano, nitro, hydroxy, aikoxy inferieur, cycloalkyle inferieur, aryle, carboxy, (aikoxy inferieur)- carbonyle, (alcenyle inferieur)oxycarbonyle, aryloxycarbonyle, (alkyle inferieur)carbonyle ou dialkylami- no, un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe aryle, ou un groupe aikoxy inferieur qui peut etre substitue avec un groupe aryle, R3 represente un atome 50 d'hydrogene, un groupe alcynyle inferieur, cycloalkyle, cycloalcenyle, aryle, oxathiinyle a substituant alkyle inferieur, uracilyle, arylcarbonyle ou benzodioxannyle, un groupe alkyle qui peut etre substitue avec un atome d'halogene ou un groupe aikoxy inferieur, cycloalkoxy, aryle, aryloxy, arylthio, cyano, carboxy ou (aikoxy inferieur)carbonyle, ou un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe carboxy, aikoxy inferieur ou alkoxycarbonyle et n a la valeur 2, 3 ou 4, 55 caracterise en ce qu'un compose represente par la formule

101 EP 0 128 006 B1

(CH ) s2 n

dans laquelle R1, R3 et n ont les memes definitions que ci-dessus, est amene a reagir avec le w pentasulfure de phosphore.

13. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule

75

(CH.J

20

dans laquelle X et Y, qui peuvent etre identiques ou differents, represented un atome d'oxygene ou de soufre ou un groupe imino et Z represente un groupe cycloalkylene, bicycloalkylene ou arylene, un groupe alkylene inferieur qui peut etre substitue avec un groupe hydroxy, alkoxy inferieur, aryle, 25 (alkyle inferieur)carbonyloxy, methylene, alkylidene, mercapto, arylcarbamoyloxy qui peuvent etre substitues, ou un groupe (alkyle inferieur)carbonylthio, un groupe alcenylene inferieur qui peut etre substitue avec un atome d'halogene ou un groupe carboxy ou aryle, ou un substituant represente par la formule -A-R- (dans laquelle A represente un atome d'oxygene ou de soufre et R represente un groupe alkylene inferieur) et n a la valeur 2, 3 ou 4, sous reserve qu'au cas ou n a la valeur 2 ou 3 et que X et 30 Y represented un atome d'oxygene, Z ne represente pas un groupe o-phenylene, caracterise en ce qu'on fait reagir une 2-cycloalcenylamine representee par la formule

35

«4-n r*>

40

dans laquelle n a la meme definition que ci-dessus, avec un compose represente par la formule

45 X

Z

50 Y

dans laquelle X, Y et Z ont la meme definition que ci-dessus, ou son anhydride.

14. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule 55

102 EP 0 128 006 B1

(CVn

dans laquelle X et Y, qui peuvent etre identiques ou differents, represented un atome d'oxygene to ou de soufre ou un groupe imino et Z represente un groupe cycloalkylene, bicycloalkylene ou arylene, un groupe alkylene inferieur qui peut etre substitue avec un groupe hydroxy, alkoxy inferieur, aryle, (alkyle inferieur)carbonyloxy, methylene, alkylidene, mercapto, arylcarbamoyloxy qui peut etre substitue ou un groupe (alkyle inferieur)carbonylthio, un groupe alcenylene inferieur qui peut etre substitue avec un atome d'halogene ou un groupe carboxy ou aryle, ou un substituant represente par la formule -A-R- 75 (dans laquelle A est un atome d'oxygene ou de soufre et R represente un groupe alkylene inferieur) et n a la valeur 2, 3 ou 4, sous reserve que lorsque n a la valeur 2 ou 3 et que X et Y representent un atome d'oxygene, Z ne soit pas un groupe o-phenylene, caracterise en ce qu'un compose represente par la formule

20

25

dans laquelle E est un atome d'halogene, un groupe (alkyle inferieur)sulfonyloxy ou benzenesulfo- nyloxy qui peut etre substitue avec un groupe alkyle inferieur et n a la meme definition que ci-dessus, 30 est amene a reagir avec un compose represente par la formule

X X Z 35 HN Y Y

40 dans laquelle X, Y et Z ont les mimes definitions que ci-dessus.

15. Procede de production d'un derive de 2-cycloalcenylamine represente par la formule

45 ^^ \ it

50

dans laquelle X est un atome d'oxygene ou de soufre ou un groupe imino, Z represente un groupe cycloalkylene, cycloalcenylene, bicycloalkylene ou arylene, un groupe alkylene inferieur qui peut etre substitue avec un groupe hydroxy, alkoxy inferieur, aryle, (alkyle inferieur)carbonyloxy, methylene, 55 alkylidene, mercapto, arylcarbamoyloxy qui peut etre substitue ou (alkyle inferieur)carbonylthio, un groupe alcenylene inferieur qui peut etre substitue avec un atome d'halogene ou un groupe carboxy ou aryle, ou un substituant represente par la formule -A-R- (dans laquelle A est un atome d'oxygene ou de soufre et R represente un groupe alkylene inferieur) et n a la valeur 2, 3 ou 4, caracterise en ce qu'un

103 EP 0 128 006 B1

compose represents par la formule

w dans laquelle X, Z et n ont les memes definitions que ci-dessus, est amene a reagir avec le pentasulfure de phosphore.

16. Procede de production d'un derive de 2-cycloalcenylamine represents par la formule 75

20

dans laquelle R4 et R5, qui peuvent etre identiques ou differents, represented un atome d'hydroge- 25 ne, un groupe nitro, cycloalkyle inferieur, aryle, dihydropyrannyle, carboxy ou acyle, un groupe alkyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe hydroxy, alkoxy inferieur, aryloxy, (alkoxy inferieur)carbonyle, di(alkyle inferieur)amino, acyle ou aryle, un groupe alcenyle inferieur qui peut etre substitue avec un atome d'halogene ou un groupe hydroxy ou aryle, ou un groupe alcynyle inferieur qui peut etre substitue avec un groupe aryle, ou bien R4 et R5 peuvent former 30 conjointement un atome d'oxygene ou de soufre, un groupe carbonyle ou un groupe alkylene ou alcenylene qui peut contenir un groupe imino et n a la valeur 2, 3 ou 4, sous reserve que les cas suivants soient exclus : lorsque n est egal a 1, R4 est un groupe butyle et R5 est un groupe hexyle ou bien R4 et R5 pris ensemble forment un groupe 2,4,4-trimethyl-1-pentenylene ; et lorsque n est egal a 2, R4 et R5, pris ensemble, forment un groupe pentylene, caracterise en ce qu'on fait reagir une 2- 35 cycloalcenylamine represented par la formule

40

45 dans laquelle n a la meme definition que ci-dessus, avec un compose carbonylique represents par la formule

50 0 = C. V

dans laquelle R4 et R5 ont les memes definitions que ci-dessus. 55 17. Procede de production du sel d'un derive de 2-cycloalcenylamine, caracterise en ce qu'un compose represents par la formule

104 EP 0 128 006 B1

dans laquelle R6 et R7, qui peuvent etre identiques ou differents, representent un atome d'hydroge- w ne, un groupe amino, alcynyle inferieur, tetrahydrofurfuryle, piperidyle, arylthio ou arylcarbonyloxy, un groupe alkyle inferieur qui est substitue avec un atome d'halogene ou un groupe cyano, nitro, alkoxy inferieur, (alkoxy inferieur)carbonyle, (alcenyle inferieur)oxycarbonyle, aryloxycarbonyle, (alkyie infe- rieur)carbonyle ou dialkylamino, un groupe alcenyle inferieur qui est substitue avec un atome d'haloge- ne ou un groupe aryle, ou un groupe alkoxy inferieur qui peut etre substitue avec un groupe aryle, et n 15 represents la valeur 1, 2, 3 ou 4, sous reserve que lorsque R6 et R7 representent un atome d'hydrogene, les sels d'acides suivants soient exclus pour chaque valeur de n : lorsque n est egal a 1 , I'acide chlorhydrique, I'acide picrique ; lorsque n est egal a 2, I'acide chlorhydrique, I'acide bromhydri- que, I'acide phosphorique, I'acide methanesulfonique, I'acide ethanesulfonique, I'acide 2-hydroxyetha- nesulfonique, I'acide (2-cyclohexenylamino)methanesulfonique, I'acide (3-cyclohexenylamino)- 20 methanesulfonique, I'acide acetique, I'acide lactique, I'acide succinique, I'acide fumarique, I'acide maleique, i'acide malique, I'acide tartrique, I'acide citrique, I'acide ascorbique, I'acide benzo'fque, I'acide salicylique, I'acide phenylacetique, I'acide mandelique, I'acide 4,4'-methylene-bis(3-hydroxy-/3- naphtoTque) ; lorsque n est egal a 3, I'acide chlorhydrique ; et lorsque n est egal a 4, I'acide picrique, est amene a reagir avec un acide inorganique, un acide organique ou un acide de Lewis. 25 Patentanspriiche

1. Bodenkrankheitsbekampfungsmittel, dadurch gekennzeichnet, da/3 es als Aktivsubstanz ein 2-Cycioal- kenylaminderivat der Formel 30

35

aufweist, worin R1 ein Wasserstoffatom, eine Hydroxy-, Amino-, niedrig Cycloalkyl-, niedrig 40 Cycloalkenyl-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylthio-, Arylcarbonyloxy- oder Arylgrup- pe, eine niedrig Alkylgruppe, die mit einem Halogenatom oder einer Cyano-, Nitro-, Hydroxy-, niedrig Alkoxy-, niedrig Cycloalkyl-, Aryl-, Carboxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert sein kann, eine niedrig Alkenylgruppe, die mit einem Halogenatom oder einer Arylgruppe substituiert sein kann, oder eine 45 niedrig Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann, bedeutet,R2 ein Wasserstoffatom, eine Hydroxy-, Amino-, niedrig Cycloalkyl-, niedrig Cycloalkenyl-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylthio-, Arylcarbonyloxy- oder Arylgruppe, eine niedrig Alkylgruppe, die mit einem Halo- genatom oder einer Cyano-, Nitro-, Hydroxy-, niedrig Alkoxy-, niedrig Cycloalkyl-, Aryl-, Carboxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder 50 Dialkylaminogruppe substituiert sein kann, eine niedrig Alkenylgruppe, die mit einem Halogenatom oder einer Arylgruppe substituiert sein kann, eine niedrig Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann oder eine Gruppe der Formel

55 O -C - RJ f

105 EP 0 128 006 B1

worin R3 ein Wasserstoffatom, eine niedrig Alkinyl-, Cycloalkyl-, Cycloalkenyl-, Aryl-, niedrig alkylsubsti- tuiertes Oxathiinyl-, Uracilyl-, Arylcarbonyl- oder Benzdioxanylgruppe, eine Alkylgruppe, die mit einem Halogenatom oder einer niedrig Alkoxy-, Cycloalkoxy-, Aryl-, Aryloxy-, Arylthio-, Cyano, Carobxy- oder niedrig Alkoxycarbonylgruppe substituiert sein kann, Oder eine niedere Alkenylgruppe, die mit einem 5 Halogenatom oder einer Carboxy-, niedrig Alkoxy- oder Alkoxycarbonylgruppe substituiert sein kann und X ein Sauerstoff- oder Schwefelatom oder eine Iminogruppe bedeuten, oder Ft3 und R1 konnen zusammengenommen eine niedere Alkyien- oder o-Phenylengruppe bedeuten oder R1 und R2 konnen zusammengenommen eine Alkyien- oder Alkenylengruppe, die ein Sauerstoff- oder Schwefelatom, eine Carbonylgruppe, eine Iminogruppe oder wenigstens einen Substituenten enthalten konnen, eine Gruppe 10 der folgenden Formel enthalten kann

— C — "7 — C — II II X Y

worin X und Y, die gleich oder verschieden sein konnen, ein Sauerstoff- oder Schwefelatom oder eine 20 Iminogruppe bedeuten und Z eine Cycloalkylen-, Cycloalkenylen, Bicycloalkylen- oder Arylengruppe, eine niedrig Alkylengruppe, die mit einem Hydroxy-, niedrig Alkoxy-, Aryl-, niedrig Alkylcarbonyloxy-, Methylen-, Alkyliden-, Mercapto- oder Arylcarbamoyloxygruppe, die substituiert sein kann, oder eine niedere Alkylcarbonylthiogruppe, eine niedrig Alkenylengruppe, die mit einem Halogenatom oder einer Carboxy- oder Arylgruppe substituiert sein kann oder einen Substituenten bedeuten kann, der durch die 25 Formel -A— R- dargestellt werden kann (worin A ein Sauerstoff- oder Schwefelatom oder eine Imino- gruppe und R eine niedere Alkylengruppe bedeuten) oder eine substituierte Alkylidengruppe der Formel

^r4 _

35 worin R* und R5, die gleich oder verschieden sein konnen, ein Wasserstoffatom, eine Nitro-, niedrig Cycloalkyl-, Aryl-, Dihydropyranyl-, Carboxy- oder Acylgruppe, eine niedrig Alkylgruppe, die mit einem Halogenatom oder einer Hydroxy-, niedrig Alkoxy-, Aryloxy-, niedrig Alkoxycarbonyl-, Di-niedrig- alkylamino-, Acyl- oder Arylgruppe substituiert sein kann, eine niedrig Alkenylgruppe, die mit einem 40 Halogenatom oder einer Hydroxy- oder Arylgruppe substituiert sein kann oder eine niedrig Alkinylgrup- pe, die mit einer Arylgruppe substituiert sein kann, bedeuten oder R* und R5 zusammengenommen eine Alkyien- oder Alkenylengruppe bedeuten konnen, die ein Sauerstoff- oder Schwefelatom, eine Carbonylgruppe oder eine Iminogruppe enthalten kann und n die Zahlen 1, 2, 3 oder 4 darstellt oder dessen Salz, und einen inerten Trager. 45 2. 2-Cycloalkenylaminderivate der Formel

50 (CVn

55 worin R2 eine Amino-, C3-Alkinyl-, C2-3-Alkoxycarbonyl-substituierte Phenylthio-, Phenylthio- oder Phenylcarbonyloxygruppe, eine Ci-5-AIkylgruppe, die mit einem Halogenatom oder Cyano-, C1-2- Alkoxy-, C2-3-Alkoxycarbonyl- oder Acetylgruppe substituiert ist, oder eine C1 -2-AIkoxygruppe bedeu-

106 EP 0 128 006 B1

tet, die mit einer Phenylgruppe substituiert sein kann und n die Zahl 2 oder 3 bedeutet.

3. 2-Cycloalkenylaminoderivat der Formel

10

worin R3 ein Wasserstoffatom, eine CsCycloalkenyl-, Benzoyl-, Benzodioxanyl-, Thienyl-, Pyridyl-, 75 Chinoxalyl-, 3-Methylbenzofuryl-, Naphthylgruppe Oder die Gruppe

20

25 eine Ci-Ci3-Alkylgruppe, die mit einem Halogenatom, einer Carboxy-, Phenyl-, 3,4-Ethylendioxyphenyl- , halogensubstituierten Phenyl-, Imidazolyl-, Triazolylgruppe, Ci -4-AIkoxy-, halogensubstituierten Phenoxy-, methylsubstituierten Phenyl-, Cyano-, C2-3-Alkoxycarbonyl-, Phenylthio- oder C3-io-Cycloal- koxygruppe substituiert sein kann, eine Phenylgruppe, die ggfs. mit einem Halogenatom, einer Hydroxy-, Nitro-, Carboxyl-, Ci-2-Alkoxy-, Phenoxy-, d-4-Alkyl-, Cyano-, C2-4-Dialkylamino- oder Ci- 30 Haloalkylgruppe substituiert sein kann, eine C2-3-Alkenylgruppe, die ggfs. mit einem Halogenatom, einer Carboxy-, C2-4.-Alkoxycarbonyl-, einer Gruppe

35

40 oder einer Ci -2-Alkoxygruppe substituiert sein kann, eine C3-6-Cycloalkylgruppe, die mit einer Carboxy-, Methyl-, Dichlorvinyl- oder Phenylgruppe substituiert sein kann, eine Furylgruppe, die mit einer Methylgruppe substituiert sein kann, eine Pyrolylgruppe, die mit einer Methylgruppe substituiert sein kann bedeutet, X bedeutet ein Sauerstoff- oder Schwefelatom und n die Zahl 2 oder 3, vorausgesetzt, da/3 die folgenden Kombinationen von n und R3 ausgeschlossen sind: 45 n = 2 und R3 = Methyl, Propyl, Phenyl, Chlormethyl, Trichlormethyl, tert-Butyl oder Trifluormethyl; n = 3 und R3= Methyl oder Trifluormethyl.

4. 2-Cycloalkenylaminderivate der Formel 50

55 (CHO

107 EP 0 128 006 B1

worin X und Y, die gleich oder verschieden sein konnen, ein Sauerstoff- oder Schwefelatom bedeuten, Z eine C3-6-Cycloalkylen-, C6-Cycloalkenylen-, C6-7 Bicycloalkylen- oder Pyridylengruppe, eine Phe- nylengruppe, die mit einem Halogenatom oder einer Nitrogruppe substituiert ist, eine C2-3-Alkylengrup- pe, die mit einer Hydroxy-, Ci-2Alkoxy-, Phenyl-, Acetoxy-, C2-3-Alkyliden-, Mercapto-, 5 Phenylcarbamoyloxy- oder Acetylthiogruppe substituiert sein kann, eine C2-Alkenylengruppe, die mit einem Halogenatom oder einer Phenylgruppe substituiert sein kann, oder einen Substituenten der Formel -A-R- (worin A ein Sauerstoff- oder Schwefelatom oder eine Iminogruppe und R eine C1-3- Alkylengruppe bedeuten) darstellen, und n die Zahl 2 oder 3 bedeutet.

10 5. 2-Cycloalkenylaminderivate der Formel

ICVn

worin R* und R5, die gleich oder verschieden sein konnen, ein Wasserstoffatom, eine Nitro-, niedrig 20 Cycloalkyl-, Aryl-, Dihydropyranyl-, Carboxy- oder Acylgruppe, eine niedere Alkylgruppe, die mit einem Halogenatom oder einer Hydroxy-, niedrig Alkoxy-, Aryloxy-, niedrig Alkoxycarbonyl-, Di-niedrig- alkylamino-, Acyl- Oder Arylgruppe substituiert sein kann, eine niedrig Alkenylgruppe, die mit einem Halogenatom oder einer Hydroxy- oder Arylgruppe substituiert sein kann oder eine niedrige Alkinyl- gruppe, die mit einer Arylgruppe substituiert sein kann, bedeuten oder R4 und R5 konnen zusammen- 25 genommen eine Alkylen- oder Alkenylengruppe bilden, die ein Sauerstoff- oder Schwefelatom, eine Carbonylgruppe oder eine Iminogruppe enthalten kann und n bedeutet die Zahl 1, 2, 3 oder 4, vorausgesetzt, da/3 die folgenden Falls ausgeschlossen sind: wenn n = 1 ist und R* eine Butylgruppe und R5 eine Hexylgruppe, oder R* und R5 zusammengenommen eine 2,4,4-Trimethyl-1-pentenylen- gruppe bilden und wenn n = 2 ist und R4 und R5 zusammengenommen eine Pentylengruppe bilden. 30 6. Verfahren zur Herstellung von 2-Cycloalkenylaminderivaten der Formel

35

40 worin R6 ein Wasserstoffatom, eine Amino-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylthio- oder Arylcarbonyloxygruppe, eine niedrig Alkylgruppe, die mit einem Halogenatom oder einer Cyano-, Nitro-, niedrig Alkoxy-, Carboxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl- , niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert ist, eine niedere Alkenylgruppe, die mit 45 einem Halogenatom oder einer Arylgruppe substituiert ist oder eine niedrige Alkoxygruppe, die ggfs. mit einer Arylgruppe substituiert ist, bedeutet, R8 bedeutet eine niedere Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylcarbonyloxy- oder Arylthiogruppe, eine niedere Alkylgruppe, die mit einem Halogenatom oder einer Cyano-, Nitro-, niedrig Alkoxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, niedrig Alkylcarbonyl-, Dialkylamino- oder Aryloxycarbonylgruppe substituiert ist, eine niedere Alkenylgruppe, 50 die mit einem Halogenatom oder einer Arylgruppe substituiert ist oder eine niedere Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann und n stellt die zahl 1 , 2,3 oder 4 dar, dadurch gekennzeich- net, da/3 man eine Verbindung der Formel

55

108 EP 0 128 006 B1

worin Rs und n die gleichen Bedeutungen haben wie oben, mit einer Verbindung der Formel w L- R8

umgesetzt wird, worin R8 die gleichen Bedeutungen hat wie oben und L ein Halogenatom, eine Arylcarbonyloxy-, Hydroxy- oder niedrig Alkylsulfonyloxygruppe Oder eine Benzolsulfonyloxygruppe, die 75 mit einer niederen Alkylgruppe substituiert sein kann, bedeutet.

7. Verfahren zur Herstellung von 2-Cycloalkenylaminderivaten der Formel

20

25 worin RG und R7, die gleich oder verschieden sein konnen, ein Wasserstoffatom, eine Amino-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylthio- oder Arylcarbonyloxygruppe, eine niedere Alkylgruppe, die mit einem Halogenatom oder einer Cyano-, Nitro-, niedrig Alkoxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert ist, 30 eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Arylgruppe substituiert ist oder eine niedere Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann, bedeuten oder RG und R7 zusammengenommen, eine Alkenylengruppe bedeuten konnen, die ein Sauerstoff- oder Schwefelatom, eine Carbonylgruppe, eine Iminogruppe oder wenigstens einen der Substituenten enthalten kann und n die Zahl 1, 2, 3 oder 4 bedeutet, vorausgesetzt, dafl der Fall ausgeschlossen ist, worin R6 und R7 35 gleichzeitig Wasserstoffatome sind, dadurch gekennzeichnet, da/3 eine Verbindung der Formel

E-N^ 40

worin R6 und R7 die gleichen Bedeutungen wie oben haben, mit einer Verbindung der folgenden 45 Formel umgesetzt wird

50

worin E ein Halogenatom, eine niedere Alkylsulfonyloxygruppe oder eine Benzolsulfonyloxygruppe 55 bedeutet, die mit einer niederen Alkylgruppe substituiert sein kann und n die gleichen Bedeutungen hat wie oben.

8. Verfahren zur Herstellung von 2-Cycloalkenylaminderivaten der Formel

109 EP 0 128 006 B1

X

w worin R1 ein Wasserstoffatom, eine Amino-.niedere Cycloalkyl-, niedere Cycloalkenyl-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylthio- oder Arylcarbonyloxygruppe, eine niedere Alkylgruppe, die mit einem Halogenatom oder einer Cyano-, Nitro-, Hydroxy-, niedrig Alkoxy-, niedrig Cycloalkyl-, Carboxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert sein kann, eine niedrig Alkenylgruppe, die mit einem Halogenatom oder 75 einer Arylgruppe substituiert sein kann, oder eine niedrige Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann, bedeutet, R3 ein Wasserstoffatom, eine niedere Alkinyl-, Cycloalkyl-, Cycloalkenyl-, Aryl-, niedrig Alkyl-substituierte Oxathiinyl-, Uracilyl-, Arylcarbonyl- oder Benzdioxanyl- gruppe, eine Alkylgruppe, die mit einem Halogenatom oder einer niederen Alkoxy-, Cycloalkoxy-, Aryl-, Aryloxy-, Arylthio-, Cyano-, Carboxy- oder niederen Alkoxycarbonylgruppe substituiert sein kann, oder 20 eine niedere Alkenylgruppe, die mit einer Carboxy- oder niederen Alkoxygruppe substituiert ist, bedeutet, X ein Sauerstoff- oder Schwefelatom oder eine Iminogruppe darstellt und n die Zahl 2, 3 oder 4 bedeutet, vorausgesetzt, da/3 wenn X ein Sauerstoffatom und R1 ein Wasserstoffatom ist, die folgenden Kombinationen von n und R3 ausgeschlossen sind: N = 2 und R3 = Methyl, Propyl, Phenyl, Chlormethyl, Trichlormethyl, tert-Butyl oder Trifluormethyl; n = 3 und R3 = Methyl oder Trifluormethyl; 25 und n = 4 und R3 = Methyl und wenn X eine Iminogruppe, R1 ein Wasserstoff und n ist 2 sind, dann ist R3 nicht eine Trichlormethylgruppe, dadurch gekennzeichnet, da/3 eine Verbindung der Formel

30

35

worin R1 und n die gleichen Bedeutungen wie oben haben, mit einer Verbindung der Formel

40 m - C - R3

45 umgesetzt wird, worin R3 und X die gleichen Bedeutungen wie oben haben und M ein Halogenatom, eine Hydroxy-, niedrig Alkoxy-, Mercapto- oder niedrig Alkylthiogruppe bedeutet oder eine Gruppe der Formel

50 -0-C-R3 t

55 (worin R3 und X die gleichen Bedeutungen wie oben haben).

9. Verfahren zur Herstellung von 2-Cycloalkenylaminderivaten der Formel

110 EP 0 128 006 B1

(CVn/ WCC \/ II II X/ 0 0

10 worin R9 ein Wasserstoffatom, eine Hydroxy-, niedrig Cycloalkyl-, niedrig Cycloalkenyl-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylthio-, Arylcarbonyloxy- oder Arylgruppe, eine niedere Alkylgruppe, die mit einem Halogenatom oder einer Cyano-, Hydroxy-, niedrig Alkoxy-, niedrig Cycloalkyl-, Aryl-, Carboxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert sein kann, eine niedere Alkenylgruppe, die mit einem Halogen- 75 atom oder einer Arylgruppe substituiert sein kann, oder eine niedrige Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann, bedeutet, Z1 eine Cycloalkenylen-, Cycloalkylen-, Bicycloalkylen oder Arylengruppe, eine niedere Alkylengruppe, die mit einer Hydroxy-, niedrig Alkoxy-, Aryl-, niedrig Alkylcarbonyloxy-, Methylen-, Alkyliden-, Mercapto-, Carbamoyloxygruppe, die substituiert sein kann, oder einer niederen Alkylcarbonylthiogruppe substituiert sein kann, oder eine niedere Alkenylengruppe, 20 die mit einem Halogenatom oder einer Carboxy- oder Arylgruppe substituiert sein kann, bedeutet und n die Zahl 2, 3 oder 4 bedeutet, dadurch gekennzeichnet, da/3 eine Verbindung der Formel

(cL V*9

30 worin R9 und n die gleichen Bedeutungen wie oben haben, mit einer Verbindung der Formel

0 35 II

0

40 umgesetzt wird, wenn Z' die gleiche Bedeutung wie oben hat.

10. Verfahren zur Herstellung von 2-Cycloalkenylaminderivaten der Formel

45

50

worin R3 ein Wasserstoffstom, eine niedere Alkinyl-, Cycloalkyl-, Cycloalkenyl-, Aryl-, niedrig Alkyl- 55 substituierte Oxathiinyl-, Uracilyl-, Arylcarbonyl- oder Benzdioxanylgruppe, eine Alkylgruppe, die mit einem Haiogenatom oder einer niederen Alkoxy-, Cycloalkoxy-, Aryl-, Aryloxy-, Arylthio-, Cyano-, Carboxy- oder niedrig Alkoxycarbonylgruppe substituiert sein kann oder eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Carboxy- oder niedrig Alkoxygruppe substituiert ist, bedeutet, X

111 EP 0 128 006 B1

ein Sauerstoff- oder Schwefelatom oder eine Iminogruppe darstellt, R10 eine niedere Cycloalkyl-, niedere Cycloalkenyl-, Arylthio-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl- oder Arylcarbonyloxy- gruppe, eine niedere Alkylgruppe, die mit einem Halogenatom Oder einer Cyano-, Hydroxy-, niedrig Cycloalkyl-, Carboxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert sein kann, oder eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Arylgruppe substituiert sein kann und n die Zahl 2, 3 oder 4 bedeuten, dadurch gekennzeichnet, da/3 eine Verbindung der Formel

10

NHCR3

75

worin R3, X und n die oben angegebenen Bedeutungen haben mit einer Verbindung der Formel

20 R10 - L'

umgesetzt wird, worin L' ein Halogenatom, eine Arylcarbonyloxy- oder niedrig Alkylsulfonyloxygruppe oder eine Benzolsulfonyloxygruppe, die mit einer niederen Alkylgruppe substituiert sein kann, bedeutet und R10 die gleiche Bedeutung wie oben hat. 25 11. Verfahren zur Herstellung von 2-CycIoalkenylaminoderviaten der Formel

30

35

worin R1 ein Wasserstoffatom, eine Amino-, niedere Cycloalkyl-, niedere Cycloalkenyl-, niedrig Alkinyl-, Tetrahydrofurfuryl-, Piperidyl-, Arylthio-, oder Arylcarbonyloxygruppe, eine niedrig Alkylgruppe, die mit einem Halogenatom oder eine Cyano-, Nitro-, Hydroxy-, niedrig Alkoxy-, niedrig Cycloalkyl-, Carboxy-, 40 niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert sein kann, eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Arylgruppe substituiert sein kann oder eine niedere Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann, bedeutet, R3 ein Wasserstoffatom, eine niedrig Alkinyl-, Cycloalkyl-, Cycloalkenyl-, Aryl-, niedrig Alkyl-substituierte Oxathiinyh Uracilyl-, Arylcarbonyl- oder Benzdioxanyl- 45 gruppe, eine Alkylgruppe, die mit einem Halogenatom oder einer niederen Alkoxy-, Cycloalkoxy-, Aryl-, Aryloxy-, Arylthio-, Cyano-, Carboxy- oder niederen Alkoxycarbonylgruppe substituiert sein kann, oder eine niedere Alkenylgruppe, die mit einer Carboxy- oder niedrig Alkoxygruppe substituiert ist, bedeutet, X ein Sauerstoff- oder Schwefelatom oder eine Iminogruppe darstellt und R3 und R1 zusammengenom- men, eine niedere Alkylen- oder o-Phenylengruppe bedeuten und n die Zahl 2, 3 oder 4 darstellt, 50 vorausgesetzt, da/3 wenn n ein Sauerstoffatom und R ein Wasserstoffatom ist, die folgenden Kombina- tionen von n und R3 ausgeschlossen sind:

n = 2 und R3= Methyl, Propyl, Phenyl, Chlormethyl, Trichlormethyl, tert-Butyl oder Trifluormethyl; n = 3 und R3= Methyl oder Trifluormethyl; und n = 4 und R3= Methyl, wenn X eine Iminogruppe, R1 ein 55 Wasserstoffatom und n = 2 sind, ist R3 nicht eine Trichlormethylgruppe, dadurch gekennzeichnet, da/3 eine Verbindung der Formel

112 EP 0 128 006 B1

10 worin R\ R3 und X die oben angegebenen Bedeutungen haben, mit einer Verbindung der Formel

20 umgesetzt wird, worin E ein Halogenatom, eine niedere Alkylsulfonyloxygruppe Oder eine Benzolsulfo- nyloxygruppe, die mit einer niederen Alkylgruppe substituiert sein kann, bedeutet und n die gleiche Bedeutung wie oben hat.

12. Verfahren zur Herstellung von 2-Cycloalkenylaminderivaten der Formel 25

30

worin R1 ein Wasserstoffatom, eine Hydroxy-, Amino-, niedrig Cycloalkyl-, niedrig Cycloalkenyl-, niedrig 35 Alkinyl-, Tetrahydrofurfuryl- Piperidyl-, Arylthio-, Arylcarbonyloxy- oder Arylgruppe, eine niedere Alkyl- gruppe, die mit einem Halogenatom oder einer Cyano-, Nitro-, Hydroxy-, niedrig Alkoxy-, niedrig Cycloalkyl-, Aryl-, Carboxy-, niedrig Alkoxycarbonyl-, niedrig Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert sein kann, eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Arylgruppe substituiert sein kann, oder eine niedere Alkoxygruppe, 40 die mit einer Arylgruppe substituiert sein kann, bedeutet, R3 ein Wasserstoffatom, eine niedere Alkinyl-, Cycloalkyl, Cycloalkenyl-, Aryl-, niedrig Alkyl-substituierte Oxathiinyl-, Uracilyl-, Arylcarbonyl- oder Benzdioxanylgruppe, eine Alkylgruppe, die mit einem Halogenatom oder einer niederen Alkoxy-, Cycloalkoxy-, Aryl-, Aryloxy-, Arylthio-, Cyano-, Carboxy- Oder niederen Alkoxycarbonylgruppe substitu- iert sein kann, oder eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Carboxy-, 45 niedrig Alkoxy- oder Alkoxycarbonylgruppe substituiert sein kann, bedeutet und n eine Zahl 2, 3 oder 4 darstellt, dadurch gekennzeichnet, da6 eine Verbindung der Formel

50

55

worin R1, R3 und n die oben angegebenen Bedeutungen haben, mit Phosphorpentasulfid umgesetzt wird.

113 EP 0 128 006 B1

13. Verfahren zur Herstellung von 2-Cycloalkenylaminderivaten der Formel

(CH.)

w die gleich oder verschieden sein konnen, ein Sauerstoff- oder Schwefelatom oder eine Iminogruppe bedeuten und Z eine Cycloalkylen-, Bicycloalkylen- oder Arylengruppe, eine niedere Alkylengruppe, die mit einer Hydroxy-, niedrig Alkoxy-, Aryl-, niedrig Alkylcarbonyioxy-, Methylen-, Alkyliden-, Mercapto-, gegebenenfalls substituierten Arylcarbamoyloxygruppe substituiert sein kann oder eine niedere Alkyl- 75 carbonylthiogruppe, eine niedere Alkenylengruppe, die mit einem Halogenatom oder einer Carboxy- oder Arylgruppe substituiert sein kann, oder ein Substituent der Formel -A-R-(worin A ein Sauerstoff- oder Schwefelatom und R eine niedere Alkylengruppe bedeuten) darstellt und n die Zahl 2, 3 oder 4 bedeutet, vorausgesetzt, da/3 ein Fall ausgeschlossen ist, worin wenn n = 2 oder 3 und X und Y Sauerstoffe sind, Z eine o-Phenylengruppe ist, dadurch gekennzeichnet, da/3 ein 2-Cycloalkenylamin 20 der Formel

25 (C»2>n

30 worin n die oben angegebene Bedeutung hat, mit einer Verbindung der Formel

35 HO

HO

40

worin X, Y und Z die oben angegebenen Bedeutungen besitzen oder einem Anhydrid davon, umgesetzt wird.

45 14. Verfahren zur Herstellung eines 2-Cycloalkenylaminderivats der Formel

50

55 worin X und Y, die gleich oder verschieden sein konnen, ein Sauerstoff- oder Schwefelatom oder eine Iminogruppe bedeuten und Z eine Cycloalkylen-, Bicycloalkylen- oder Arylengruppe, eine niedere Alkylengruppe, die mit einer Hydroxy-, niedrig Alkoxy-, Aryl-, niedrig Alkylcarbonyioxy-, Methylen-,

114 EP 0 128 006 B1

Alkyliden-, Mercapto- einer ggfs. substituierten Arylcarbamoyloxygruppe oder einer niederen Alkylcar- bonylthiogruppe substituiert sein kann, eine niedere Alkenylengruppe, die mit einem Halogenatom oder einer Carboxy- oder Arylgruppe substituiert sein kann, oder einen Substituenten dep Formel -A-R- (worin A ein Sauerstoff- oder Schwefelatom und R eine niedere Alkylengruppe bedeutet) bedeuten kann und n die Zahl 2, 3 oder 4 darstellt, vorausgesetzt, da/3 wenn n = 2 oder 3 und X und Y ein Sauerstoffatom sind, Z keine o-Phenylengruppe bedeutet, dadurch gekennzeichnet, daC eine Verbin- dung der Formel w

15

worin E ein Halogenatom, eine niedere Alkylsulfonyloxygruppe oder eine Benzolsulfonyloxygruppe, die mit einer niederen Alkylgruppe substituiert sein kann, bedeutet und n die gleiche Bedeutung wie oben hat, mit einer Verbindung der Formel 20

X A 25 HN\/ Y Y

30 umgesetzt wird, worin X, Y und Z die oben angegebenen Bedeutungen haben.

15. Verfahren zur Herstellung eines 2-Cycloalkenylaminderivats der Formel

35 ^y^ \ i,

40

worin X ein Sauerstoff- oder Schwefelatom oder eine Iminogrupppe bedeutet, Z eine Cycloalkylen-, Cycloalkenylen-, Bicycloalkylen- oder Arylengruppe, eine niedere Alkylengruppe, die mit einer Hydroxy- einer substitu- , niedrig Alkoxy-, Aryl-, niedrig Alkylcarbonyloxy-, Methylen-, Alkyliden-, Mercapto-, ggfs. 45 ierten Arylcarbamoyloxygruppe oder einer niederen Alkylcarbonylthiogruppe substituiert sein kann, eine niedere Alkenylengruppe, die mit einem Halogenatom oder einer Carboxy- oder Arylgruppe substituiert sein kann, oder einem Substituenten der Formel -A-R-(worin A ein Sauerstoff- oder Schwefelatom und R eine niedere Alkylengruppe bedeutet) darstellt und n die Zahl 2, 3 oder 4 bedeutet, dadurch gekennzeichnet, dafi eine Verbindung der Formel 50

(CH )n

115 EP 0 128 006 B1

worin X, Z und n die gleichen Bedeutungen wie oben haben, mit Phosphorpentasulfid umgesetzt wird.

16. Verfahren zur Herstellung eines 2-Cycloalkenylaminderivats der Formel

w

worin R* und R5, die gleich oder verschieden sein konnen, ein Wasserstoffatom, eine Nitro-, niedere Cycloalkyl-, Aryl-, Dihydropyranyl-, Carboxy- oder Acylgruppe, eine niedere Alkylgruppe, die mit einem 75 Halogenatom oder einer Hydroxy-, niedrig Alkoxy-, Aryloxy-, niedrig Alkoxycarbonyl-, Di-niedrig- alkylamino-, Acyl- oder Arylgruppe substituiert sein kann, eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Hydroxy- oder Arylgruppe substituiert sein kann oder eine niedere Alkinylgrup- pe, die mit einer Arylgruppe substituiert sein kann, bedeuten oder R* und R5 zusammengenommen ein Sauerstoff- oder Schwefelatom, eine Carbonylgruppe oder eine Alkylen- oder Alkenylengruppe, die eine 20 Iminogruppe enthalten kann, bedeuten und n die Zahlen 1, 2, 3 oder 4 darstellt, vorausgesetzt, da/3 die folgenden Fallen ausgeschlossen sind: wenn n = 1 , ist R4 eine Butylgruppe und R5 eine Hexylgruppe, oder R4 und R5 .zusammengenommen, bilden eine 2,4,4-Trimethyl-1-pentenylengruppe; und wenn n = 2 ist, bilden R4 und Rs, zusammengenommen, eine Pentylengruppe, dadurch gekennzeichnet, dafl 2- Cycloalkenylamin der Formel 25

30

worin n die oben angegebene Bedeutung hat, mit einer Carbonylverbindung der Formel 35 R4

VR 40

worin R4 und R5 die oben angegebenen Bedeutungen haben, umgesetzt wird.

17. Verfahren zur Herstellung des Salzes eines 2-Cycloalkenylaminderivats, dadurch gekennzeichnet, dafl 45 eine Verbindung der Formel

50 (CHJ

55 worin R5 und R7, die gleich oder verschieden sein konnen, ein Wasserstoffatom, eine Amino-, niedere Alkinyl, Tetrahydrofurfuryl-, Piperidyl-, Arylthio- oder Arylcarbonyloxygruppe, eine niedere Alkylgruppe, die mit einem Halogenatom oder einer Cyano-, Nitro-, niedrig Alkoxy-, niedrig Alkoxycarbonyl-, niedrig

116 EP 0 128 006 B1

Alkenyloxycarbonyl-, Aryloxycarbonyl-, niedrig Alkylcarbonyl- oder Dialkylaminogruppe substituiert sein kann, eine niedere Alkenylgruppe, die mit einem Halogenatom oder einer Arylgruppe substituiert ist, oder eine niedrig Alkoxygruppe, die mit einer Arylgruppe substituiert sein kann, bedeuten und n die RG R7 Wasserstoffatom Zahl 1 , 2, 3 oder 4 darstellt, vorausgesetzt, da/3 wenn sowohl als auch ein sind, 5 Salze mit den folgenden Sauren fur folgende Werte von n ausgeschlossen sind; wenn n = 1 ist: Salzsaure, Pikrinsaure; wenn n = 2: Salzsaure, Bromwasserstoffsaure, Phosphorsaure, Methansulfon- saure, Ethansulfonsaure, 2-Hydroxyethansulfonsaure, (2-Cyclohexenylamino)methansulfonsaure, (3-Cy- clohexenylamino)methansulfonsaure, Essigsaure, Milchsaure, Bernsteinsaure, Fumarsaure, Maleinsau- re, Apfelsaure, Weinsaure, Zitronensaure, Ascorbinsaure, Benzoesaure, Salicylsaure, Phenylessigsau- w re, Mandelsaure, 4,4 '-Methylenbis-(3-hydroxy-C-naphthoesaure); wenn n = 3: Salzsaure und wenn n = 4: Pikrinsaure; mit einer anorganischen, organischen oder Lewissaure umgesetzt wird.

75

20

25

30

35

40

45

50

55

117