JPH0456821B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to new acrylic acid amides, their preparation, and their use as biocides. The new acrylic acid amides have the following formula: In the formula, A is a group , B represents the group Y-(CR ₅ = CR ₆ )k- (), and Q represents the group and , X represents O, S or NH, Y represents a C _3-10 alkyl group, or k is 1 or 2
represents a C _1-2 alkyl group, or represents a substituted C _1-10 alkyl group, or represents a C _3-7
represents an optionally substituted group selected from the group consisting of alkenyl, C _3-7 cycloalkyl, C _5-7 cycloalkenyl, pyridyl, furyl, thienyl, α- and β-naphthyl, or the group CR _{a 5-} to 7-membered ring, preferably a saturated alicyclic group, or a group on which a benzene ring may be fused together with 5; , k represents a number of 0.1 or 2, m represents a number of 1, 2, 3 or 4, n represents a number of 0 or 1, R ₁ represents hydrogen, C _1-4 alkyl, cyano and if k is 0 it also represents chlorine, bromine or iodine, R ₂ and R ₁₁ are hydrogen, halogen, nitro, C 1-4 alkyl or C _1-4 alkyl optionally mono- or polysubstituted with fluorine or chlorine. alkoxy,
C _3-4 alkynyloxy, amino, NH (C _1-4 alkyl), N (C _1-4 alkyl) ₂ , cyano, phenyl,
C _3-6 cycloalkyl, C _3-4 alkenyloxy, hydroxy (C _1-4 alkyl), NHCOR ₆ , CO ₂ R ₆ ,
CONR ₇ R ₈ , or C _2-8 alkyl interrupted with oxygen, or R ₃ , R ₄ , R ₁₂ and R ₁₃ are hydrogen, halogen, C _1-4
Alkyl, C _1-4 alkoxy, (C _1-4 alkyl)-S
(O) _p (p=0, 1 or 2), represents hydroxy or (C _1-4 acyl)oxy, or R ₃ /R ₄ and R ₁₂ /R ₁₃ are both adjacent 2 on the phenyl ring.
represents methylenedioxy or ethylenedioxy bonded to the atom, R ₅ and R ₆ represent hydrogen or C _1-4 alkyl,
or R ₅ represents a 5- to 7-membered ring, preferably a saturated alicyclic group, to which a benzene ring may be fused together with the C atom to which it is bonded and Y;
R ₇ and R ₈ represent C _1-4 alkyl, C _3-7 cycloalkyl, phenyl, benzyl, furfuryl, tetrahydrofurfuryl or C _3-4 alkenyl, or R ₇ may be hydrogen or both may be O, NR ₆ or S-(O)q (q = 0, 1 or 2) can represent an optionally interrupted C _3-5 alkylene chain, R ₉ and R ₁₀ are both R ₇ and R ₈ of one type. present only when representing a chain and represents hydrogen or C _1-4 alkyl, provided that A and B cannot simultaneously represent a group selected from the group consisting of phenyl, monohalophenyl, mononitrophenyl and monoaminophenyl . Compounds of the above formula may optionally also exist in the form of acid addition salts. Within the scope of the above definitions, the various groups may be the same or different. Y is a substituent in the given group, in particular halogen, nitro, amino, C _1-4 alkyl and alkoxy groups optionally mono- or polysubstituted by halogen, NH (C _1-4 alkyl) and N
(C _1-4 ) ₂ , and also phenoxy, phenylthio and C _1-4 alkylthio. The carbon chain of the alkyl, alkoxy, alkyl-S(O) _p , mono- or dialkylamino group preferably contains 1-3, more preferably 1 or 2 carbon atoms. If the carbon chains contain three or more carbon atoms, they can be either straight or branched. By halogen is meant fluorine, chlorine, bromine and iodine, especially chlorine and bromine. The group A is preferably di- or tri-substituted and contains two substituents, such as methyl, methoxy, ethyl, ethoxy, fluorine, chlorine, bromine, CF ₃ ,
_CF2Cl , _CF3O , _CH3S , _CH3SO , _{CH3SO2 ,
NH2} , _NHCH3 ,N( _CH3 ) ₂ ,O- _CH2 -O,O
_{-C2H4 -} O is preferably present in the 3 and 4 positions. Q preferably represents a group of the formula in which R ₇
and R ₈ both represent an optionally interrupted alkylene chain and thus represent, for example, the group: [Formula] [Formula] [Formula] [Formula] If A and B in the formula are different, then the compounds of the formula may represent cis-trans isomers. In this case, the formula includes individual isomers and mixtures of cis and trans compounds. The novel compounds are obtained by methods known per se. (a) Equation (wherein A, B and R ₁ are as defined above), or a reactive derivative thereof, optionally prepared in situ, can be synthesized with the formula H-Q (), where Q is as defined above. ) or optionally purified in situ.
react with an activated derivative (in this case the acid itself is used). The method thus consists of the acylation of a compound with a carboxylic acid of the formula or with a reactive derivative of said carboxylic acid in the presence of an acid activating or dehydrating agent, or the acylation of an amino group with a reactive derivative of an amine. The reaction of a compound of formula with a carboxylic acid of formula in the presence of an activating reagent.
A final product is obtained in which X represents oxygen. Examples of reactive derivatives of carboxylic acids of formula optionally prepared in the reaction mixture are alkyl, aryl, aralkyl esters thereof such as methyl, ethyl, phenyl or benzyl esters; imidazolides; acid chlorides or bromides. acid halides; acid anhydrides; mixed acid anhydrides with aliphatic or aromatic carboxylic acids, sulfenic acids, sulfinic acids, sulfonic acids or carbonic esters, such as acetic acid, propionic acid, p-toluenesulfonic acid or O-ethyl carbonic acid; or its N-hydroxyimide. Suitable reactive derivatives of amines of formula optionally prepared in the reaction mixture include, for example, phosphorus azo derivatives. The nature of the hydrocarbon radicals in the groups mentioned above is not particularly important. Alkyl groups generally contain 6 to 12 carbon atoms, may be straight-chained or branched, and may be interrupted with oxygen or sulfur. Aryl groups may preferably contain 6 to 10 carbon atoms, aralkyl groups may contain 7 to 12 carbon atoms, while alkyl moieties contain 1 to 6 carbon atoms, and aryl The moiety may be substituted by C _1-3 alkyl (in which case the aryl-substituted alkyl group will contain correspondingly fewer carbon atoms).
The aromatic ring can also optionally bear mixed substituents, such as one or more C _1-2 alkyl groups, C _1-2 alkoxy groups and/or one or more halogen atoms. Examples of acid activators and/or dehydrating agents are chloroformic acid esters such as chloroformic acid ethyl ester, phosphorus pentoxide, N,N'-dicyclohexylcarbodiimide, N,N'-carbonyldiimidazole, N,N'- Contains thionyldiimidazole. The reaction is carried out in a solvent or mixed solvent such as methylene chloride, chloroform, carbon tetrachloride, ether, tetrahydrofuran, dioxane, benzene, toluene, acetonitrile or dimethylformamide, optionally with an inorganic base such as sodium carbonate, or triethylamine or a solvent. in the presence of a tertiary organic base such as pyridine, which also acts as It is preferably carried out at temperatures between. It is not necessary to isolate the reactive derivatives of the compound of the general formula or which may form in the reaction mixture, and the reaction can also be carried out in excess of the compound of the formula as solvent. (b) Eq. (In the formula, A and B are the same as above.) (In the formula, R ₁ and Q are the same as above,
R and R′ are the same or different and represent a straight-chain or branched C _1-12 alkyl group, a C _7-12 aralkyl group or a C _6-12 aryl group, and the alkyl chain is interrupted by O or S. Aryl and aralkyl groups may also be mono- or polysubstituted on the nucleus by halogen, C _1-2 alkyl or alkoxy. ) with a phosphonic acid derivative. The alkyl chains may be interrupted with oxygen or sulfur, and the aryl and aralkyl groups may be mono- or polysubstituted in the nucleus by halogen, C _1-2 alkyl or alkoxy. The reaction is carried out in the presence of a basic substance such as sodium hydroxide, potassium tert-butoxide, sodium methoxide or sodium amide.
Preferably tetrahydrofuran, dioxane,
from 0°C to 150°C, preferably from 0°C to the boiling point of the reaction mixture, in a solvent sufficiently inert to the reaction conditions, such as 1,2-dimethoxyethane, dimethylformamide, benzene, toluene or a mixture of such solvents. It is carried out at temperatures between . An excess of compound XI can also be used as reaction medium. (c) To prepare compounds of the formula in which X represents sulfur (thioamides), the corresponding amides are reacted with phosphorus pentasulfide in an inert solvent. Suitable solvents include, for example, toluene, xylene or benzene. Reaction temperature is generally 120℃
, but between 0° C. and the boiling point of the reaction mixture. (d) To produce a compound (amidine) of the formula in which X represents NH, the corresponding iminoesters, the formula (In the formula, A, B, R and R ₁ are the same as above.)
is reacted with an amine of formula. The reaction is carried out in an inert solvent such as ether or tetrahydrofuran at a temperature between about 0°C and 100°C. (e) k represents zero (in the group), R ₁ is halogen,
In particular, to prepare compounds of the formula representing chlorine or bromine, the halogen is added to the double bond of acrylic acid in the corresponding starting material, and the hydrogen halide is then eliminated under heating. The reaction is carried out in an inert solvent such as permanent acetic acid or preferably with the addition of hydroacetic acid at about 30°C.
It is carried out at temperatures between 100°C. (f) To prepare compounds of the formula in which R ₁ represents CN, the corresponding compounds in which R ₁ represents halogen can be reacted with copper cyanide () in an inert solvent. Suitable inert solvents include, for example, dimethylformamide and dimethylsulfoxide. The reaction temperature is preferably 70°C to 180°C. (g) To prepare a compound of the formula in which R ₁ represents NC, the ketone of formula (In the formula, Z represents a group Z or represents a group OR, and R is the same as above.) The reaction is carried out in an inert solvent such as benzene or toluene, preferably using a water separator and in the presence of a catalyst such as ammonium acetate/permanent acetic acid, under heat, preferably at the boiling point of the reaction mixture. If in the compound Z
If represents a group OR, this is replaced by a group Q according to method (a). (h) In order to produce compounds in which the radicals A and/or B contain optionally acylated phenolic hydroxyl groups, the radicals A and/or B contain lower to intermediate (C _{1 -12} ) Corresponding compounds of the formula containing an alkoxy or benzyloxy group can be ether-cleaved and optionally subsequently acylated. Ether splitting is carried out with conventional reagents such as hydrogen bromide/hydroacetic acid under heat. Reactive derivatives of the acid to be introduced, such as acid chlorides and acid anhydrides, can be used for the acylation. (i) To prepare compounds of the formula in which A and/or B contain an amino group, the corresponding nitro compounds can be reduced in a conventional manner. The reducing agent is, for example, sodium dithionite and the reaction medium is an inert solvent, for example ethanol/
It can be water. The reaction temperature is from ambient temperature to about 100°C. The mixture of cis and trans isomers obtained in the present invention can be resolved into the corresponding cis and trans isomers by conventional methods, if desired. Separation of isomers can be done using fractional crystallization, e.g. methanol,
It is carried out by crystallization from ethanol, isopropanol, methanol/water or ethanol/petroleum ether. Compounds of the formula with a basic group can be converted into acid addition salts, preferably hydrochlorides, hydrobromides, sulfates or phosphates, if desired. The starting materials are known or can be prepared in conventional manner analogously to known compounds, but
Compounds of the formula in which B represents a group and k represents 1 or 2 can be obtained, for example, by the following reaction formula. In these formulas, A, R, R', R ₁ , R ₅ , R ₆
and Y are as defined above and R preferably represents a lower alkyl group, such as methyl or ethyl. The olefination of compound B to compound C is carried out, for example, using the Horner modification of the Witschig reaction. Ketones of formula Obtained by oxidation with chromium oxide, elimination of the acetyl group and subsequent halogenation. The starting material of the formula in which A and B represent phenyl groups is the corresponding benzophenone of the formula (wherein R, R' and R ₁ are as defined above, and R'' represents a lower alkyl group) in the presence of a base, and the ester group is subsequently hydrolyzed. formula (wherein A, B, R ₁ and R are as defined above), the required starting compound is It can also be obtained by the Liformatsky method according to the following. formula (wherein A, R ₁₁ , R ₁₂ and R ₁₃ are as defined above) is the formula and obtained following saponification. The compounds according to the invention are useful in particular for phytopathogenic fungi, in particular downy mildew, pseudodowny molds (Plasmopara and
Phytophthora), scarf, gray mold,
and highly effective against rust and mold. Because they have very low phytotoxicity, the new compounds can be used in virtually all utilitarian and ornamental plant crops, such as maize, wheat, rye,
It can be used in cereals such as oats and rice, tomatoes, cucumbers, beans, potatoes, beets, and in viticulture and fruit cultivation, and in roses, carnations and chrysanthemums. The new compound acts on the leaves and has a systemic effect. For this reason, the use of active substances against Plasmopara
Some of the compounds according to the invention used for foliar treatment at concentrations of 20 to 100 ppm (e.g. Examples 1, 5, 11, 13, 21, 23, 37, 38, 43, 78,
Compounds 90, 104, 105, 109, 121, 125 and 127) completely killed the mold.
For eradication of Phytophthora, active substances (e.g. Examples 6, 21, 24, 35, 37, 39, 40, 50,
65, 88, 101, 105, 106, 114, 125, 127, 130,
100 ppm or often less of compounds 149, 157, 162) is sufficient for a satisfactory effect. It is often advantageous to use the compounds of the invention in combination with known antifungal active substances. The combined effect, if any, is clearly greater than the pure additive effect. Combination partners Manganese ethylene-bis-dithiocarbamate (Maneb) Manganese ethylene-bis-thiodicarbamate (Mancozeb) Zinc ethylene-bis-dithiocarbamate (Zineb) N-Trichloromethylthio-tetrahydrophthalimide (Captan) N-Trichlormethylthiophthalimide (Folpet) N-(1,1,2,2-tetrachloroethylthio)tetrahydrophthalimide (Captafol) 2,3-dicyano-1,4-dithianthraquinone (Dithianon) (N,N'-propylene-bis- Zinc dithiocarbamate (Proineb) Copper oxychloride Sodium 4-dimethylaminobenzenediazosulfonate (Fenaminosulf) Triphenyltin acetate (Fentinacetat) Triphenyltin hydroxide (Fentinhydroxyd) Iron dimethyldithiocarbamate (Ferbam) N-(2-furoyl )-N-(2,6-xylyl)
-DL-Alanine (Furalaxyl) 3-(dimethylamino)propylcarbamate (Propamocarb) N-Ethyl-N-(3-dimethylamino)thiocarbamate (Prothiocarb) Tetramethylthiuram disulfide (Thriram) N-Dichlorofurormethylthio -N,N'-dimethyl-N-p-tolyl-sulfamide N-(2-methoxyacetyl)-N-(2,6-
(xylyl) aniline (Metalaxyl) Zinc dimethylthiocarbamate (Ziram) N-Dichlorofluoromethylthio-N',N'-dimethyl-N-phenylsulfamide (Dichlofluamid) 3-Trichloromethyl-5-ethoxy-1,
2,4-thiadiazol (Etridazol) Tri[amino-zinc-ethylene-bis-(dithiocarbamate)]tetrahydro-1,2,4,
7-Dithiadiazolene-3,8-dithione polymer (Metiram) Tris(o-ethyl phosphate)-aluminum (Phosethyl) 2-Cyano-N-(ethylcarbamoyl)-2-
Cymoxanil N-(3-chlorophenyl)-N-tetrahydrofuran-2-one-3-yl)-cyclopropanecarbonamide (Cyprofuran) Tetrachlor-isophthalodinitrile (Cylorothalonil) 6-Methyl -2-Oxo-1,3-dithio[4,5-b]quinoxaline (Chinomethionate) 4-Cyclododecyl-2,6-dimethylmorpholine (Dodemorph) 1-Dodecylguanidinium acetate (Dodin) Diisopropyl-5-nitro Isophthalate (Nitrothal-isopropyl) 2,4-dichloro-α-(pyrimidin-5-yl)benzhydryl alcohol (Fenarimol) 1-(β-allyloxy-2,4-dichlorophenethyl)imidazole (Imazalil) 3 -(3,5-dichlorophenyl)-N-isopropyl-2,4-dioxoimidazoline-1-carboxamide (Iprodion) Sulfur 2,3-dihydro-6-methyl-5-phenylcarbamoyl-1,4-oxythiine- 4,4-
Dioxide (Oxycarboxin) N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide (Procymidon) 6-Ethoxycarbonyl-5-methylpyrazolo[1,5-d]pyrimidine-2 -il-0,0-
Dimethylphosphorus thioate (Pyrazophos) 2-(thiazol-4-yl)-benzimidazol (Thiabendazol) 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazole-1- )
-2-Butanone (Triadimefon) 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazol-1-yl)
-2-Butanol (Triadimenol) 3-(3,5-dichlorophenyl)-5-methyl-5-vinyloxyzolidine-2,4-dione (Vinclozolin) Methylbenzimidazol-2-ylcarbamate (Carbendazin) 2,4 ,6-trimethyl-N-phenyl-3-
Furancarboxamide (Methfuroxam) β-[1,1'-biphenyl]-4-yl-oxy)-α-(1,1-dimethylethyl)-1H-1,
2,4-Triazole-1-ethanol (Bitertanol) 2-(2-furyl)benzimidazole (Fuberidazol) 5-Butyl-2-ethylamino-6-methylpyrimidin-4-ol (Ethirimol) 2-Methyl-3- Fluanilide (Fenfuram) Bis-(8-guanidino-octyl)amine (Guazatin) N-cyclohexyl-N-methoxy-2,5-
Dimethylfuran-3-carboxylic acid amide (Furmecyclox) 2-chloro-4'-furor-α-(pyrimidine-
5-yl)benzhydryl alcohol (Nuarimol) Methyl-1-(butylcarbamoyl)benzimidazole carbamate (Benomyl) 0,0-diethylphthalimidophosphonothioate (Dithalin) 7-bromo-5-chloroquinolin-8-yl-
Acrylate (Halacrimat) 1-[2-(2,4-dichlorophenyl)-4-
Propyl-1,3-dioxolan-2-ylmethyl]1H-1,2,4-triazole (Propiconazol) Dimethyl-4,4'-(o-phenylene)bis(3-thioallophanate) (Thiophanat-
methyl) 1,4-bis(2,2,2-trichloro-1-
Formamidoethyl) piperazine (Triforine) 2,6-dimethyl-4-tridecylmorpholine (Tridemorph) 4-[3-[4-(1,1-dimethyl-ethyl)
Phenyl]-2-methyl]-propyl 2,6-(cis)-dimethylmorpholine (Fenpropemorph) 1-[2-(2,4-cyclophenyl)-4-
Ethyl-1,3-dioxolan-2-ylmethyl]1H-1,2,4-triazole (Etaconazol) 1-[1-(2,4-chlorophenyl)-4,4
-dimethyl-3-hydroxy-2-pentyl]
1,2,4-triazole (Diclobutrazol) 2,4-dichloro-6-(2-chloroanilino)
-1,3,5-triazine (Anilazin) 2-iodo-N-phenylbenzamide (Benodanil) 2-sec. Butyl-4,6-dinitrophenyl,
-Methylcrotonate (Binapacryl) 5-Butyl-2-(ethylamino)-6-methyl-4-pyrimidylmethylsulfosate (Buprimate) 2,4-dinitro-6-octylphenylcrotonate (Dinocap) 5 ,6-dihydro-2-methyl-1,4-oxathiin-3-carbanilide (Carboxin) N-propyl-N-[(2,4,6-trichlorophenoxy)-2-ethyl]-imidazole-1-
Carboxamides (Prochloraz) For plant protection applications, the new compounds can be combined with excipients and/or processed as a unit. If they are used in combination with other active substances, they can be prepared in combinations or, for example, in tank mixtures. If necessary, the concentrate is diluted with water to create a spray solution containing about 0.001 to 1% by weight of active material before use. For use as low volume or very low volume formulations, the content of active substance can be quite high (up to 20 or 90% by weight, respectively). Examples of formulations according to the invention: 1 Suspended powder compound 20 parts by weight kaolin 20 Sodium sulfate 5 Calcium carbonate 2 Calcium ligninsulfonate 9 Sodium diisobutylnaphthalene sulfonate
1 〃 Silicic limestone 43 〃 Ingredients are crushed. For use, the composition is suspended in water at an active substance concentration of about 0.001 to 0.5% by weight. 2 Concentrated emulsion type compound 13% by weight Dodecylbenzenesulfonic acid triethylamine salt 10 Dimethylformamide 75 The following examples illustrate the preparation according to the invention. Preparation of starting materials: 4'-chloro-4-nitrobenzophenone 100 g of 4-nitrobenzoyl chloride (0.54
A mixture of 100 g (0.75 mol) of aluminum chloride and 100 ml of chlorobenzene (111 g (0.99 mol)) is heated to 80° C. with stirring to remove moisture from the air and melt. After the evolution of hydrogen chloride has ceased, the temperature is increased to 100° C. and the mixture is stirred at this temperature for a further half hour. After cooling to about 40-50°C, the viscous liquid reaction mixture is poured onto water,
The white precipitate formed is suction filtered and washed with ethanol. mp100-102℃ 4-Amino-4'-chlorobenzophenone A hot aqueous solution of 13 g (0.05 mol) of 4'-chloro-4-nitrobenzophenone in 80 ml of ethanol is chlorinated in small portions with stirring in 50 ml of concentrated hydrochloric acid. When added to a hot solution of 53.5 g (0.24 mol) of tin() dihydrate, it reacts violently. After adding everything,
The mixture is heated on a steam bath for 2 hours and then stirred into the aqueous potassium hydroxide solution. The precipitate that forms is filtered off with suction and dissolved in boiling ethanol. Insoluble matter is filtered out and the filtrate is cooled. The precipitated bright yellow crystals are filtered off with suction. mp184-185℃ 4-amino-3,4',5-trichloro-benzophenone 4-amino-4'-chloro-benzophenone 23.2
g (0.1 mol) is dissolved in 200 ml of tetrahydrofuran. To this solution are added 400 ml of glacial acetic acid, and then a solution of 14.2 g (0.2 mol) of chlorine in 150 ml of glacial acetic acid is quickly added thereto with vigorous stirring and under ice cooling. Stir the mixture for another 5 minutes and pour into the water. A white precipitate is obtained, which is filtered off with suction and crystallized from ethanol. mp 165-167°C 4,4'-Diacetamino-diphenylmethane 76 g (1 mol) of methylal is added to 260 g (2 mol) of aniline hydrochloride dissolved in 600 ml of water with stirring. After all additions, heat the mixture to 60°C for 1
time and then heated to 90° C. for 3 hours, during which time the methanol formed is distilled off. After cooling, the solution is mixed with a concentrated solution of 40 g of sodium hydroxide while cooling with ice. An oil precipitates out, which crystallizes on further stirring. The crystals are filtered off with suction and partitioned between chloroform 2 and 10N sodium hydroxide solution. The chloroform solution is separated, dried over sodium sulphate and evaporated to dryness under reduced pressure. The residue is dissolved in benzene 1 and mixed with petroleum ether until the oily impurities are separated off. The benzene-petroleum ether solution remaining after decanting is poured into about 1 liter of petroleum ether with stirring to precipitate 4,4'-diamino-diphenylmethane as an oil. This fractional precipitation was repeated twice. The oily 4,4'-diamino-diphenylmethane thus obtained was dissolved in as little amount of glacial acetic acid as possible, and 205 g (2 mol) of acetic anhydride was added dropwise to it with stirring.
The resulting mixture is heated to 120°C for 1 hour. After cooling, the mixture is poured into about 3 ml of water, and the precipitated crystals are filtered and washed with water. mp228-230℃ 4,4'-Diamino-benzophenone Dissolve 100 g of chromic anhydride in 50 ml of water and make up the mixture to 240 ml with glacial acetic acid. 97 ml of this solution is slowly added to a solution of 77 g of 4,4'-diacetaminodiphenylmethane while stirring and cooling, taking care that the temperature does not rise above 40°C. The mixture is then heated to 90°C for 1 hour with stirring, cooled and poured into ice water. An oily product precipitates and crystallizes on standing for a while. Suction filter the precipitated crystals, wash with water, and add 92 ml of 66% sulfuric acid.
Heat for 5 minutes at reflux temperature in a vacuum chamber. After cooling, they are poured into water and the aqueous solution is made alkaline with 10N sodium hydroxide solution to precipitate the crude 4,4'-diamino-benzophenone. mp247-248℃ 4,4'-Diamino-3,3',5,5'-tetrachloro-benzophenone 4,4'-diamino-benzophenone 25g (0.12
25 ml of concentrated hydrochloric acid, 200 ml of water and 500 ml of glacial acetic acid
Dissolve in the mixture. While stirring vigorously and cooling with ice water, add 400 ml of glacial acetic acid to this solution.
Quickly combine with a solution of 33.5 g (0.42 mol) of chlorine in the solution, stir for a further 2 minutes, pour onto ice, filter the precipitate with suction and crystallize from ethanol/water. mp, 237-239°C Note: The isomer whose =CH- CO protons are seen at low field strength in the NMR spectrum was designated as isomer A. Example 1 (a) 4-amino-β-(4-chlorophenyl)-
3,5-dichlorocinnamic acid ethyl ester 13.2 g sodium hydride (26.4 g 50% oil suspension) in 50 ml dry 1,2-dimethoxyethane
(0.55 mol) of 1,2-dimethoxyethane while stirring and drying under ice cooling.
Diethylphosphonoacetic acid ethyl ester in 108
g (0.55 mol) of the solution is slowly added dropwise, and the mixture foams vigorously. After all additions are complete, stir the mixture for an additional 30 minutes. 4 in 800 ml of dry 1,2-dimethoxyethane.
A suspension of 150 g (0.5 mol) of -amino-3,4',5-trichlorobenzophenone is combined and heated at reflux temperature for 1 hour, giving a clear solution. The solution is evaporated to dryness under reduced pressure and the residue is partitioned between chloroform and water. Dry the chloroform phase;
Evaporate to dryness under reduced pressure. After mixing with 150 ml of ethanol, crystallization begins. Suction and filter the crystals.
Wash with ethanol and petroleum ether. mp88-110°C NMR spectrum of mixture of isomers A and B ( _CDCl3 , _60MH2 ): =CH - CO-
6.27 ppm singlet) 6.23 ppm singlet) (1 proton) Pure isomer A is obtained after two recrystallizations from ethanol/petroleum ether. mp124−125
℃ NMR spectrum (CDCl ₃ , 60MH ₂ ):=C
H-Co-6.27ppm singlet (1 proton) (b) 4-amino-β-(4'-chlorophenyl)-
3,5-dichlorocinnamic acid 4-amino-β-(4'-chlorophenyl)-
136 g (0.368 mol) of 3,5-dichlorocinnamic acid ethyl ester (mixture of isomers A and B) was added to 1000 ml of ethanol and 5N sodium hydroxide solution.
Reflux for 1 hour in a mixture with 300 ml. After cooling, the mixture is diluted with water and acidified with 2N hydrochloric acid. Initially an oily product precipitates and crystallizes after a while. The crystals are filtered off with suction and recrystallized from ethanol. Colorless crystals of pure isomer A are obtained. mp241-243℃ (decomposition) NMR spectrum (DMSO, 60MH ₂ ):=C
H-CO-6.37 ppm singlet (1 proton) Other crystal fractions are obtained by further concentrating the mother liquor. mp200-204℃ Consists of isomer A/B=1/1.5. NMR spectrum (DMSO, 60MH ₂ ):=C
H-CO-6.37ppm singlet) 6.29ppm singlet) (1 broton) (c) 4-amino-β-(4-chlorophenyl)-
3,5-dichlorocinnamic acid morpholide 4-amino-β(4-chlorophenyl)3,
5-dichlorocinnamic acid (1 of isomers A and B:
1.5 Mixture) 20g (0.058 mol) is dissolved in 700ml of dry chloroform. With ice cooling and stirring, 5.93 g (0.058 mol) of triethylamine are added, the mixture is cooled to -10°C and combined with 6.35 g (0.058 mol) of ethyl chloroformate. After addition, add morpholine under further stirring and cooling.
Add 25.5g (0.29 mole). The mixture is stirred for a further 4 hours at room temperature, extracted three times with water, and the organic phase is dried over sodium sulphate and evaporated to dryness under reduced pressure. The residue is chromatographed on a silica gel column (silica gel: substance = 10:1; eluent chloroform/ethyl acetate = 1:1). The eluates containing the substance are combined and evaporated to dryness under reduced pressure.
Colorless crystals containing a mixture of cis/trans isomers in a ratio of 3:2 with mp 140-144 DEG C. are obtained. NMR spectrum (CDCl ₃ , 80MH ₂ := CH
-CO-6.2 ppm singlet) 6.14 ppm singlet) (1 proton) Recrystallization of the cis/trans mixture from ethanol gives the pure trans isomer with mp 168-171°C. NMR spectrum (CDCl ₃ , 80MH ₂ ):=C
H-CO-6.2ppm singlet (1 proton)
The formula produced in this way The configuration of the compound is ¹ H− in 90MH ₂
It was elucidated by NMR spectrum analysis. This shows the following signals. (a) H _A of the 4-amino-3,5-dichlorophenyl ring, 7.09 ppm (singlet) (b) H _A ′ and H _B ′ of the 4-chlorophenyl ring,
7.23 ppm (doublet) and 7.33 ppm (doublet) (c) H _C of the olefin, 6.22 ppm (singlet) (the olefinic H of the isomeric compound (isomer B) is as established by the spectrum of the isomer mixture. (observed at 6.17 ppm) NOE measurement (The N uclear O verhauser
Effect, RESchirmer, Academic Press New
York and London1971). NOE measurements are performed on _{a 90MH2} FT NMR instrument (Bruker
Model HX-90/15″) was used.
Homonuclear NOE measurements in the ¹ H-NMR spectrum at 90MH ₂ gave the following results. [Table] These intensity measurements (Table) show that the steric spacing between H _C and H _A is substantially smaller than that between H _C and H _A '.
Thus, the compound of the above formula exists in the trans form shown in the formula. Example 2 4-amino-β-(4'-chlorophenyl)-3,
5-Dichlorocinnamic acid morpholide A solution of 5.3 g (0.02 mol) of diethylphosphonoacetic acid morpholide in 100 ml of dry tetrahydrofuran is
Add slowly dropwise with stirring to 1 g of sodium hydride (0.02 mol, 50% in oil) suspended in 50 ml of dry tetrahydrofuran. Mild heat generation and strong foaming occur. After all additions, stir the mixture for another 10 minutes. 4 in 20ml dry tetrahydrofuran
A solution of 3 g (0.01 mol) of -amino-3,4',5-trichlorobenzophenone is added dropwise to the resulting clear solution and the mixture is heated to reflux temperature for 16 hours. After cooling, pour into water and thoroughly extract with methylene chloride. The methylene chloride phase is dried over sodium sulfate and evaporated to dryness under reduced pressure. The residue is crystallized from isopropanol/petroleum ether. mp150−
Colorless crystals containing cis/trans isomers in a ratio of 1:3 are obtained at 155°C. NMR spectrum (CDCl ₃ , 80MH ₂ ):= CH
-CO-6.2 ppm singlet) 6.14 ppm singlet) (1 proton) Recrystallization of the cis/trans mixture from ethanol gives the pure trans isomer with mp 168-171°C. NMR spectrum (CPCl ₃ , 80MH ₂ ):= CH
-CO-6.2ppm singlet (1 proton) Example 3 4-amino-β(4'-chlorophenyl)-3,5
-dichlorocinnamic acid morpholide 4-amino-3,4',5-trichlorobenzophenone and diethylphosphonoacetic acid morpholide,
It was prepared in the same manner as in Example 2 from potassium tert-butoxide in dimethylformamide. Purified by column chromatography and crystallization from isopropanol/petroleum ether. m of a 1:3 mixture of cis/trans isomers.
p.150-155℃ NMR spectrum (CPCl ₃ , 80MH ₂ ):= CH
-CO-6.2ppm singlet) 6.14ppm singlet) (1 proton) Example 4 trans-4-amino-β-(4'-chlorophenyl)-3,5-dichlorocinnamic acid morpholide 4-amino-β-(4' -chlorophenyl)-3,
It was produced in the same manner as in Example 3 from 5-dichlorocinnamic acid isomer A, ethyl chloroformate, and morpholine. mp168−171℃ NMR spectrum (CDCl ₃ , 80MH ₂ ):= CH
-CO-6.2ppm singlet (1 proton) Example 5 4-Amino-β-(4'-amino-3',5'-dichlorophenyl)-3,5-dichlorocinnamic acid morpholide Diethylphosphonoacetic acid morpholide 16.2 g
(0.061 mol) is dissolved in 100 ml of dry tetrahydrofuran. Sodium hydride (55% oil suspension)
2.7g) Add 1.5g (0.061 mol) to it in small amounts. After all additions, stir the mixture for another 30 minutes. Then it was converted into 4,4′-diamino-3,3′,5,
Combine with a solution of 18 g (0.051 mol) of 5'-tetrachlorobenzophenone and reflux for 18 hours. After cooling, the solution is poured into water/ice and thoroughly extracted with a total of 2 portions of methylene chloride. The methylene chloride phase is dried over sodium sulfate and concentrated under reduced pressure. Dilute the residue with methylene chloride
Suspend in 200ml and boil briefly. After cooling, filter the crystalline material with suction. mp, 256-258℃ Example 6 4-amino-β-(4'-bromphenyl)-3,
5-dibromocinnamic acid morpholide 4-amino-β-(4'-bromphenyl)-3,
5-dibromocinnamic acid (isomer A:B=1.5:1)
, ethyl chloroformate, triethylamine,
It was produced in the same manner as in Example 3 from morpholine. mp165- of a 2.5:1 mixture of isomers A and B
180℃ NMR spectrum (CDCl ₃ , 80MH ₂ ):= CH
-CO-6.25ppm singlet) 6.20ppm singlet) (1 proton) Example 7 4-amino-β-(4'-chlorophenyl)-3,
5-dibromocinnamic acid morpholide 4-amino-β-(4'-chlorophenyl)-3,
5-dibromocinnamic acid (isomer A:B=5:1)
, ethyl chloroformate, triethylamine,
It was prepared in the same manner as in Example 1c) from morpholine. mp178- of a 6:1 mixture of isomers A and B
189℃ NMR spectrum (CDCl ₃ , 80MH ₂ ):= CH
-CO-6.22ppm singlet) 6.18ppm singlet) (1 proton) Example 8 4-amino-3,5-dibromo-β-(4'-florphenyl)cinnamic acid morpholide 4-amino-3,5-dibrome-β -(4'-florphenyl)cinnamic acid (isomer A:B=2.5:1)
, ethyl chloroformate, triethylamine,
It was prepared in the same manner as in Example 1c) from morpholine. mp186- of a 4:1 mixture of isomers A and B
197°C NMR spectrum (CDCl ₃ , MH ₂ ):= CH −
CO-6.21ppm singlet) 6.16ppm singlet) (1 proton) Example 9 4-Amino-3,5-dibromo-β-phenylcinnamic acid morpholide 4-Amino-3,5-dibromo-β-phenylcinnamic acid (isomer It was prepared in the same manner as in Example 1c) from compound A:B=1:1), ethyl chloroformate, triethylamine and morpholine. mp156- of a 1:1 mixture of isomers A and B
174℃ NMR spectrum (CDCl ₃ , 400MH ₂ ):= CH
-CO-6.2ppm singlet) 6.18ppm singlet) (1 proton) Example 10 4-amino-β-(4'-bromphenyl)-3,
5-dichlorocinnamic acid morpholide 4-amino-β-(4'-bromphenyl)-3,
5-dichlorocinnamic acid (isomer A:B=1:2.5)
, ethyl chloroformate, triethylamine,
It was prepared in the same manner as in Example 1c) from morpholine. mp188-194°C NMR spectrum of pure isomer A (CDCl ₃ , 60MH ₂ ):= CH
-CO-6.23ppm singlet) (1 proton) Example 11 4-Amino-3,5-dichloro-β-(4'-florphenyl)cinnamic acid morpholide 4-amino-3,5-dichloro-β-(4' -florphenyl) cinnamic acid (isomer A:B=3:1),
It was produced in the same manner as in Example 1(c) from ethyl chloroformate, triethylamine, and morpholine. mp160-176°C NMR spectrum of a 3:1 mixture of _isomers A and B ( _CDCl3,60MH2 ):= CH-
CO-6.23ppm singlet) 6.18ppm singlet) (1 proton) Example 12 4-Amino-3,5-dichloro-β-phenylcinnamic acid morpholide 4-Amino-3,5-dichloro-β-phenylcinnamic acid isomer Example 1 from A:B=1.5:1), ethyl chloroformate, triethylamine, morpholine
(c) Produced in the same manner. mp143- of a 1:1 mixture of isomers A and B
160℃ NMR spectrum (CDCl ₃ , 60MH ₂ ):= CH
-CO-6.2ppm singlet) 6.18ppm singlet) (1 proton) Example 13 (a) 3-bromo-4-dimethylaminobenzophenone 4-dimethylaminobenzophenone 22.5g
(0.1 mol) is dissolved in 60 ml of acetic acid. Within 1 hour, 5.3 ml (0.105 mol) of bromine in 20 ml of acetic acid are added dropwise to it with stirring. Add more mixture
Stir for 30 minutes, add a little water and a little sodium bisulfite for decolorization. The grease thus obtained is shaken with toluene/water, the toluene phase is washed twice with water, dried and the toluene is distilled off under reduced pressure. Yield 24.4g (theoretical 80
%); viscous oil (b) 3-bromo-4-dimethylamino-β-phenylcinnamic acid Sodium hydride (contains 20% paraffin oil)
Stir 2.1 g (0.07 mol) with 30 ml of anhydrous 1,2-dimethoxyethane. While cooling with ice water, a solution of 15.7 g (0.07 mol) of triethylphosphonoacetate in 30 ml of 1,2-dimethoxyethane was added dropwise until a clear solution was formed.
18.25 3-bromo-4-dimethylaminobenzophenone dissolved in 30 ml of 2-dimethoxyethane
g (0.06 mol). The mixture was refluxed for 4 hours and after standing overnight the solvent was removed under reduced pressure. The residue is shaken with toluene/water, the toluene phase is washed again with water, dried and the toluene is removed under reduced pressure. The residue was dissolved in a methanolic potassium hydroxide solution (14 g (0.25 mol) of potassium hydroxide, 250 ml of methanol, and water).
25 ml) and saponified by refluxing for 2 hours. Concentrate the solution under reduced pressure and shake the residue with toluene/water. The aqueous solution is adjusted to pH 6.5 by adding hydrochloric acid and the substance precipitates in solid form. It is soluble in excess hydrochloric acid. Dry after washing with water. Yield 15.2g (73% of theory) mp147℃ (c) 3-Bromo-4-dimethylamino-β-phenylcinnamic acid morpholide 5.19 g (15 mmol) of 3-bromo-4-dimethylamino-β-phenylcinnamic acid is dissolved in 30 ml of anhydrous tetrahydrofuran, and 3.24 g (20 mmol) of 1,1'-carbonyldiimidazole is added in small portions. After the CO ₂ evolution has ended and a clear solution is obtained, 1.74 g (20 mmol) of morpholine are added and the mixture is left at room temperature for 10 minutes and then refluxed for 30 minutes. Concentrate the solution under reduced pressure and shake the residue with toluene/water. The toluene phase is washed two more times with water, dried and concentrated under reduced pressure. The resulting oil crystallizes when kneaded with a small amount of methanol. Yield 6.25 g (91.5% of theory) mp 169° C. Rf: 0.55 (toluene/acetone 70:30) According to the invention and according to the examples given above, the compounds in the table below are obtained. [Table] [Table] [Table] *Rf value: Eluent toluene/acetone 7:3;
Polygram TLC plates manufactured by Macherey-Nagel (serial number 805021) were used; 22°C Example 38 3-(3,4-dimethoxyphenyl)-5-phenylpenta-2,4-diene-1-carboxylic acid morpholide ( a) 3,4-dimethoxy-β-methylcinnamic acid ethyl ester Stir 24.75 g (825 mmol) of sodium hydride (containing 20% paraffin oil) with 300 ml of anhydrous 1,2-dimethoxyethane, and add triethylphosphonoacetate while cooling with ice water.
Drop 185 g (825 mormil). 3,4-dimethoxyacetophenone 135g (750mmol)
is added all at once to the clear solution and the mixture is refluxed for 3 hours with stirring on a boiling water bath. After standing overnight, 1,2-dimethoxyethane was distilled off under reduced pressure.
The residue is extracted with toluene/water. The toluene solution is washed again with water, dried and the toluene is removed under reduced pressure. The residue is fractionally distilled under reduced pressure. Yield 159 g (85% of theory) Bp 130°C/0.04 mbar (b) 3-(3,4-dimethoxyphenyl)-5-phenylpenta-2,4-diene-1-carboxylic acid Dissolve 5.05 g (45 mmol) of potassium tert-butoxide in 20 ml of anhydrous dimethylformamide and dissolve 3,4 in 10 ml of anhydrous dimethylformamide.
-dimethoxy-β-methylcinnamic acid ethyl ester 10.0 g (40 mmol) and benzaldehyde
4.78 g (45 mmol) of the solution are added dropwise to the ice bath while stirring. The mixture is stirred for a further 4 hours at room temperature, combined with water and acidified with hydrochloric acid. Stir the resulting grease with hot water and add sodium carbonate in portions until a solution is obtained. This aqueous solution is extracted twice with toluene. The substance precipitates when acidified with hydrochloric acid and is recrystallized from toluene after washing with water. Yield 9.7g (78% of theory) mp164℃ (c) 3-(3,4-dimethoxyphenyl)-5-phenylpenta-2,4-diene-1-carboxylic acid morpholide Dissolve 4.66 g (15 mmol) of 3-(3,4-dimethoxyphenyl)-5-phenylpenta-2,4-diene-1-carboxylic acid in 30 ml of anhydrous tetrahydrofuran, and dissolve 3.24 g of 1,1'-carbonyldiimizosol. (20 mmol) in portions. After the evolution of CO ₂ has ceased and a clear solution is obtained, 1.74 g (20 mmol) of morpholine are added and the mixture is left at room temperature for 10 minutes and then refluxed for 30 minutes. The solution is concentrated by evaporation under reduced pressure and the residue is shaken with toluene/water. The toluene solution is washed twice with water, dried and concentrated by vacuum evaporation. Yield 4.9g (86% of theory). Pure oil by TLC. Rf: 0.54 (toluene/acetone 70:30) Analysis: Calculated value C 72.80%, experimental value 73.12% Calculated value H 6.64%, experimental value 6.67% Calculated value N 3.69%, experimental value 3.64% Example 39 (a) 5 -(4-chlorophenyl)-3-(3,4-
dimethoxyphenyl)-hexa-2,4-diene-1-carboxylic acid Dissolve 5.05 g (45 mmol) of potassium tert-butoxide in 20 ml of anhydrous dimethylformamide and dissolve 3,4 in 10 ml of anhydrous dimethylformamide.
A solution of 10.0 g (40 mmol) of -dimethoxy-β-methylcinnamic acid ethyl ester and 6.96 g (45 mmol) of 4-chloroacetophenone is added dropwise to the ice bath while stirring. The mixture is stirred for a further 4 hours at room temperature, mixed with water and acidified with hydrochloric acid. Stir the resulting viscous oil with hot water and add sodium carbonate in portions until a solution is obtained. Wash the aqueous solution once with toluene. When acidified with hydrochloric acid, the substance is obtained in the form of an oil. Extract this with toluene, wash the extract twice with water,
Dry and remove toluene under reduced pressure. Yield 11.9 g (83% of theory) (b) 5-(4-chlorophenyl)-3-(3,4-
dimethoxyphenyl)-hexa-2,4-diene-1-carboxylic acid morpholide 5-(4-chlorophenyl)-3-(3,4-
5.38 g (15 mmol) of hexa-2,4-diene-1-carboxylic acid (dimethoxyphenyl)
Dissolve in 30 ml of anhydrous tetrahydrofuran and add 3.24 g of 1,1'-carbonyldiimidazole to it.
(20 mmol) in portions. After the CO ₂ evolution has ceased, 1.74 g (20 mmol) of morpholine are added and the mixture is left at room temperature for 10 minutes and then refluxed for 30 minutes. Concentrate the solution under reduced pressure and shake the residue with toluene/water. The toluene phase is washed again with water, dried and concentrated under reduced pressure to approximately 20 ml. This solution is purified using a chromatography column packed with 30 g of silica gel mixed with toluene. Elution was first with toluene and then with a toluene/acetone mixture (90:
10). Fractions containing substances with Rf 0.47 (toluene/acetone 70:30 on a silica gel plate) are collected and concentrated under reduced pressure. Yield 4.7g (73% of theory); Oil analysis: Calculated value C 67.36%, experimental value 67.38% Calculated value H 6.12%, experimental value 6.22% Calculated value N 3.27%, experimental value 3.13% Example 40 (a) 3-(3,4-dimethoxyphenyl)-2-methylcrotonic acid ethyl ester Sodium hydroxide (contains 20% paraffin oil)
3.3 g (110 mmol) are stirred with 40 ml of anhydrous 1,2-dimethoxyethane and 26.2 g (110 mmol) of triethyl-2-phosphonopropinate are added dropwise thereto while cooling with ice water. After a clear solution is obtained, 18 g (100 mmol) of 3,4-dimethoxyacetophenone are added and the mixture is refluxed for 3 hours with stirring. After leaving it overnight,
The 1,2-dimethoxyethane is removed under reduced pressure and the residue is shaken with toluene/water. The toluene phase is washed again with water, dried and the toluene is removed under reduced pressure. The residue is fractionally distilled under reduced pressure. Yield 19.8 g (81% of theory) Bp145°C/0.4 mbar (b) 5-(4-chlorophenyl)-3-(3,4-
dimethoxyphenyl)-2-methyl-penta-
2,4-diene-1-carboxylic acid 6.17 g (55 mmol) of potassium tert-butoxide was dissolved in 20 ml of anhydrous dimethylformamide, and 3-
(3,4-dimethoxyphenyl)-2-methylcrotonic acid ethyl ester 13.2 g (50 mmol)
and 7.73 g of 4-chlorobenzaldehyde (55
(mmol) solution is added dropwise to the ice bath while stirring. The mixture is stirred for a further 6 hours at room temperature, mixed with water and acidified with hydrochloric acid. Stir the resulting grease with hot water and add sodium carbonate in small portions until a solution forms. This aqueous solution is extracted once with toluene. The oil obtained upon acidification with hydrochloric acid is recrystallized from toluene/petroleum ether. Yield 11g (61% of theory) mp164℃ (c) 5-(4-chlorophenyl)-3-(3,4-
dimethoxyphenyl)-2-methyl-penta-
2,4-diene-1-carboxylic acid morpholide 5-(4-chlorophenyl)-3-(3,4-
dimethoxyphenyl)-2-methylpenta-2,
Dissolve 5.38 g (15 mmol) of 4-diene-1-carboxylic acid in 30 ml of anhydrous tetrahydrofuran, and dissolve 3.24 g of 1,1'-carbonyldiimidazole.
(20 mmol) is added to it little by little. _CO2
After the evolution had ended, 1.74 g (20 mmol) of morpholine was added and the mixture was left at room temperature for 10 min.
Reflux for 2 hours. Concentrate the solution under reduced pressure and shake the residue with toluene/water. The toluene phase is washed again with water, dried and concentrated under reduced pressure to approximately 20 ml. This solution is purified using a chromatography column packed with 30 g of silica gel mixed with toluene. Elution is carried out first with toluene and then with a toluene/acetone mixture (90:10). Collect fractions containing substances with Rf0.52 (toluene/acetone 70:30),
Evaporate under reduced pressure. Yield 4.95g (77% of theory); Oil analysis: Calculated value C 67.36%, experimental value 67.71% Calculated value H 6.12%, experimental value 6.10% Calculated value N 3.27%, experimental value 3.36% Example 41 5-( 4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-penta-2,4-diene-1-carxylic acid morpholide (a) 3,4-dimethoxyacetophenone 215.9 g (2.75 mol) of acetyl chloride Veratrol suspended in 1400 ml of ethylene chloride
Pour into 345.5g (2.5mol). Mixture at room temperature
Stir for 30 minutes, cool with ice/salt, then
Add 366.6 g (2.75 moles) of AlCl ₃ . temperature 15
Stir the mixture for 3 hours while maintaining the temperature below °C. After extraction and distillation using a rotary evaporator, 419.1 g (93% of theory) of oil with a bp of 125-127° C./0.5 mbar are obtained.
CCl ₄ /petroleum ether gives a material with mp 48-50°C. (b) 3,4-dimethoxy-β-methylcinnamic acid ethyl ester 291.17 g of potassium tertiary butoxide suspended in 1.7 g of anhydrous 1,2-dimethoxyethane
(2.6 mol) Hetriethylphosphonoacetate
576.2 g (2.57 mol) are added, the mixture is stirred for 15 minutes, and then 463 g (2.57 mol) of oily 3,4-dimethoxyacetophenone is added thereto.
Stir the mixture at about 60°C for 7 hours. The solvent is removed using a rotary evaporator and the residue is mixed with water and extracted with ether. 3,4-
Dimethoxy-β-methylcinnamic acid ethyl ester is isolated from the ether phase in a yield of 558 g (87% of theory). bp137℃/0.17 mbar(c) 3-(3,4-dimethoxyphenyl)-5-
(4-Chlorphenyl)-penta-2,4-diene-1-carboxylic acid Potassium tertiary in 75 ml of dimethylformamide
28.1 g (0.25 mol) of 1-butoxide are prepared. Dimethylformamide at 10-15℃
30.7g of 4-chlorobenzaldehyde in 125ml
(0.22 mol) and 3,4-dimethoxy-β-
Methyl cinnamic acid ethyl ester 50g (0.20mol)
Add to it within 10 minutes while cooling. The mixture is stirred for 45 minutes without cooling, mixed with 350 ml of water and acidified with 50 ml of 6N hydrochloric acid. The precipitated product is filtered with suction and recrystallized from dioxane. Yield 57.6 g (84% of theory) mp226-227°C (d) 3-(3,4-dimethoxyphenyl)-5-(4
-Chlorphenyl)-penta-2,4-diene-1-carboxylic acid morpholide 2.38 g (17.3 mmol) of phosphorus trichloride are added to 4.52 g (52 mmol) of morpholine in 15 ml of pyridine for 10 minutes with cooling to -5 to 0°C. Drip within. After a further half hour of reaction at room temperature, 12.1 g (35 mmol) of the acid obtained in step (c) suspended in 35 ml of pyridine are added all at once. The mixture is left at room temperature for 3 hours and then stirred for a further half hour at 40°C.
The mixture is combined with ice and concentrated hydrochloric acid until a strongly acidic solution is obtained. The reaction product is precipitated by addition of ethyl acetate. It is filtered with suction, washed with water and ethyl acetate and recrystallized from isopropanol/water. Yield 12.3g (85% of theory) mp125-126℃ Example 42 3-(3,4-methylenedioxyphenyl)-5
-(4-Chlorphenyl)-penta-2,4-diene-1-carboxylic acid isopropylamide (a) 3-(3,4-methylenedioxyphenyl)-
5-(4-chlorophenyl)-penta-2,4-
Diene-1-carboxylic acid 29 g (0.26 mol) of 4-chlorobenzaldehyde and 3,4-carboxylic acid in 160 ml of dimethylformamide
55 g (0.235 mmol) of methylenedioxy-β-methylcinnamic acid ethyl ester are added to a suspension of 35 g (0.25 mol) of potassium tert-butoxide in 80 ml of dimethylformamide under cooling within 10 minutes until the temperature reaches above 20°C. Add so that it does not become
After stirring for 1 hour without cooling, water and hydrochloric acid are added (until an acidic reaction mixture results) and the precipitate formed is filtered off with suction. It can be recrystallized from large amounts of isopropanol. Yield 67.8g (87% of theory) mp205−206℃ (b) 3-(3,4-methylenedioxyphenyl)−
5-(4-chlorophenyl)-penta-2,4-
Diene-1-carboxylic acid isopropylamide 5.9 g of isopropylamine in 25 ml of pyridine
(0.10 mol) and 4.6 g (0.034 mol) of phosphorus trichloride in a conventional manner to produce a phosphazo compound. 22.0 g (0.067 mol) of the acid obtained in (a)
Add and stir the mixture for 4 hours and leave overnight. After addition of ice and acidification with hydrochloric acid, extraction is carried out with ethyl acetate, the extract is washed with water and dilute sodium hydroxide solution, dried and concentrated by evaporation. The residue can be recrystallized from benzene/petroleum ether. Yield 10.8g (43.5% of theory) mp125-127℃ The Rf values in the table below are from Macherey Nagel.
Determined on TLC plates (serial number 805021). Eluent toluene/acetone 7:3, 22°C The following compounds are obtained according to the examples. [Table] [Table] [Table] [Table] [Table] Example 93 Example 94 2-Cyano-3-(3,4-dimethoxyphenyl)-3-phenyl acrylic acid morpholide 3,4-dimethoxybenzophenone 12.1 g (50
mmol), cyanoacetomorpholine 8.48g (55
mmol), glacial acetic acid 10g, ammonium acetate 4g
and 100 ml of benzene in a water separator while stirring. After 5, 10 and 15 hours, 4 g of ammonium acetate and 5 g of glacial acetic acid are added in each case. . The mixture is heated for a total of 20 hours and the benzene and glacial acetic acid are distilled off using a rotor evaporator. Shake the residue with toluene/water, wash the organic phase again with water,
Dry and concentrate under reduced pressure. This concentrate is purified on a silica gel column. Elution is carried out first with toluene and then with a toluene/acetone mixture 80:20.
The fraction containing the material with Rf 0.56 (toluene/acetone 70:30) is completely evaporated under reduced pressure. Yield 7.7g (51% of theory); viscous yellow oil E/Z ratio 50:50 Analysis: Calculated value C 69.83%, Experimental value 69.64% H 5.86% 6.07% N 7.40% 7.66% Example 95 3- (3-acetamino-4-methoxyphenyl)
-3-Phenyl acrylic acid morpholide 3-(3-amino-4-methoxyphenyl)-3
- 3.38 g (10 mmol) of phenylacrylic acid morpholide was dissolved in 20 ml of acetic anhydride and heated on a boiling water bath for 4 hours.
Heat for an hour. The solution is concentrated under reduced pressure and the residue is recrystallized from ethyl acetate/petroleum ether. Yield 3.1g (81.5% of theory), mp97℃ Rf value 0.50 (toluene/acetone 30:70) Analysis: Calculated value C69.46%, experimental value 69.67% H 6.39%, 6.48% N 7.37%, 7.24% Example 96 3-(3-amino-4-methoxyphenyl)-3
-Phenyl acrylic acid morpholide 3-(4-methoxy-3-nitrophenyl)-3
- 7.37 g (20 mmol) of phenylacrylic acid morpholide are dissolved in 100 ml of ethanol, 100 ml of water are added, then the mixture is heated to 50° C. and 14.7 g (70 mmol) of sodium dithionite are added with stirring. The mixture is refluxed for 1 hour, the ethanol is removed under reduced pressure and water is added. The resulting brown grease is dissolved in toluene and purified on a silica gel column. Elution is carried out first with toluene and then with a toluene/acetone mixture 80:20. The fraction containing the substance with Rf0.26 (toluene/acetone 70:30) is concentrated under reduced pressure. Yield 4.4g (65% of theory; viscous oil E/Z ratio
30:70 Analysis: Calculated value C70.98%, experimental value 71.06% H 6.55%, 6.68% N 8.28%, 8.02% Example 97 3-(4-methoxy-3-methylphenyl)-3
-Phenylthioacrylic acid morpholide 3-(4-methoxy-3-methylphenyl)-3
- 6.75 g (20 mmol) of phenyl acrylic acid morpholide and 2.22 g of fine (ground) phosphorus pentasulfide
(10 mmol) is refluxed with 50 ml of anhydrous xylene for 3 hours. After cooling, insoluble matter is filtered, and the filtrate is washed with water, dried, and concentrated under reduced pressure. This concentrate is purified on a silica gel column. Elution is carried out first with toluene, then with a triene/diisopropyl ether mixture 90:10 and then 80:20. The fraction containing the substance with Rf 0.59 (toluene/diisopropyl ether 1:1) is concentrated under reduced pressure, and the yellow oil obtained is heated and dissolved in cyclohexane. Cooling causes the substance to crystallize. Yield 4.0g (56.5% of theory), mp125-127℃ Analysis: Calculated value C71.35%, experimental value 71.52% H6.56%, 6.59% N9.07%, 8.98% Others that can be produced by the present invention The compounds are listed in the table below. [Table] [Table] [Table] [Table] [Table] [Table] [Table] [Table] [Table] [Table]

Claims (1)

[Claims] 1. A compound of the following formula and optionally an acid addition salt of the compound: [In the formula, A is a group , B represents the group Y-(CR ₅ = CR ₆ ) _k − ...(), and Q represents the group and , X represents O, S or NH, Y represents a C _3-10 alkyl group, or further represents a C _1-2 alkyl group when k is equal to 1 or 2, or is substituted represents a C _1-10 alkyl group, or C _3-7 alkenyl, C _3-7 cycloalkyl, C _5-7 cycloalkenyl, pyridyl, furyl, thienyl,
represents an optionally substituted group selected from the group consisting of α- and β-naphthyl;
represents a 5- to 7-membered ring, preferably a saturated alicyclic group, to which a benzene ring may be fused together with CR ₅ , or a group , k represents the number 0, 1 or 2, m represents the number 1, 2, 3 or 4, n represents the number 0 or 1, R ₁ is hydrogen, C _1-4 alkyl, represents cyano, and if k is 0 also represents chlorine, bromine or iodine; R ₂ and R ₁₁ are C _1-4 mono- or polysubstituted with hydrogen, halogen, nitro, optionally fluorine or chlorine; alkyl or alkoxy,
C _3-4 alkynyloxy, amino, NH (C _1-4 alkyl), N (C _1-4 alkyl) ₂ , cyano, phenyl,
C _3-6 cycloalkyl, C _3-4 alkenyloxy, hydroxy (C _1-4 alkyl), NHCOR ₆ , CO ₂ R ₆ ,
CONR ₇ R ₈ , or C _2-8 alkyl interrupted with oxygen, or R ₃ , R ₄ , R ₁₂ and R ₁₃ are hydrogen, halogen,
C _1-4 alkyl, C _1-4 alkoxy, (C _1-4 alkyl)
-S(O) _P (p=0, 1 or 2), represents hydroxy or (C _1-4 acyl)oxy, or R ₃ /
R ₄ and R ₁₂ /R ₁₃ both represent methylenedioxy or ethylenedioxy bonded to two adjacent atoms on the phenyl ring, R ₅ and R ₆ represent hydrogen or C _1-4 alkyl,
R ₅ can also represent a 5- to 7-membered ring, preferably a saturated alicyclic group, to which a benzene ring may be fused together with the C atom to which it is bonded and Y, and R ₇ and R ₈ are C represents _1-4 alkyl, C _3-7 cycloalkyl, phenyl, benzyl, furfuryl, tetrahydrofurfuryl or C _3-4 alkenyl,
Alternatively, R ₇ may be hydrogen, and both may be O, NR ₆
or can represent a C _3-5 alkylene chain, which may be interrupted by S(O) _q (q=0, 1 or 2), and R ₉ and R ₁₀ are both R ₇ and R ₈ of one type of chain. and represents hydrogen or C _1-4 alkyl, provided that A and B cannot simultaneously represent a group selected from the group consisting of phenyl, monohalophenyl, mononitrophenyl and monoaminophenyl. ]. 2. A compound according to claim 1, wherein X represents oxygen. 3 Q is the formula (In the formula, R ₉ and R ₁₀ are the same as defined above.) The compound according to claim 1 or 2, wherein R 9 and R 10 are the same as defined above. 4 Claims 1, 2 or 3, wherein A represents a phenyl group substituted at the 3 and 4 positions
compound of term. 5. A compound according to any one of claims 1 to 4, wherein R ₁ is hydrogen. 6. A compound according to any one of claims 3 to 5, wherein R ₉ and R ₁₀ are hydrogen. 7 Compound of the following formula or optionally an acid addition salt of the compound [In the formula, A is a group , B represents the group Y-(CR ₅ = CR ₆ ) _k − (), and Q represents the group and , X represents O, S or NH, Y represents a C _3-10 alkyl group, or further represents a C _1-2 alkyl group when k is equal to 1 or 2, or is substituted represents a C _1-10 alkyl group, or C _3-7 alkenyl, C _3-7 cycloalkyl, C _5-7 cycloalkenyl, pyridyl, furyl, thienyl,
represents an optionally substituted group selected from the group consisting of α- and β-naphthyl;
represents a 5- to 7-membered ring, preferably a saturated alicyclic group, to which a benzene ring may be fused together with CR ₅ , or a group , k represents the number 0, 1 or 2, m represents the number 1, 2, 3 or 4, n represents the number 0 or 1, R ₁ is hydrogen, C _1-4 alkyl, represents cyano, and if k is 0 also represents chlorine, bromine or iodine; R ₂ and R ₁₁ are C _1-4 mono- or polysubstituted with hydrogen, halogen, nitro, optionally fluorine or chlorine; alkyl or alkoxy,
C _3-4 alkynyloxy, amino, NH (C _1-4 alkyl), N (C _1-4 alkyl) ₂ , cyano, phenyl,
C _3-6 cycloalkyl, C _3-4 alkenyloxy, hydroxy (C _1-4 alkyl), NHCOR ₆ , CO ₂ R ₆ ,
CONR ₇ R ₈ , or C _2-8 alkyl interrupted with oxygen, or , R ₃ , R ₄ , R ₁₂ and R ₁₃ are hydrogen, halogen,
C _1-4 alkyl, C _1-4 alkoxy, (C _1-4 alkyl)
-S(O) _P (p=0, 1 or 2), represents hydroxy or (C _1-4 acyl)oxy, or R ₃ /
R ₄ and R ₁₂ /R ₁₃ both represent methylenedioxy or ethylenedioxy bonded to two adjacent atoms on the phenyl ring, R ₅ and R ₆ represent hydrogen or C _1-4 alkyl,
In addition, R ₅ can also represent a 5- to 7-membered ring, preferably a saturated alicyclic group, to which a benzene ring may be fused together with the C atom to which it is bonded and Y, and R ₇ and R ₈ are C represents _1-4 alkyl, C _3-7 cycloalkyl, phenyl, benzyl, furfuryl, tetrahydrofurfuryl or C _3-4 alkenyl,
Or R ₇ may be hydrogen, and both may be O, NR ₆
or can represent a C _3-5 alkylene chain, which may be interrupted by S(O) _q (q=0, 1 or 2), and R ₉ and R ₁₀ are both R ₇ and R ₈ of one type of chain. and represents hydrogen or C _1-4 alkyl, provided that A and B cannot simultaneously represent a group selected from the group consisting of phenyl, monohalophenyl, mononitrophenyl and monoaminophenyl. ] Biocides, especially fungicides, characterized in that they contain customary excipients and/or carriers. 8 Compounds of the following formula and optionally acid addition salts of the compounds [In the formula, A is a group , B represents the group Y-(CR ₅ = CR ₆ ) _k − (), and Q represents the group and , X represents O, S or NH, Y represents a C _3-10 alkyl group, or further represents a C _1-2 alkyl group when k is equal to 1 or 2, or is substituted represents a C _1-10 alkyl group, or C _3-7 alkenyl, C _3-7 cycloalkyl, C _5-7 cycloalkenyl, pyridyl, furyl, thienyl,
represents an optionally substituted group selected from the group consisting of α- and β-naphthyl;
represents a 5- to 7-membered ring, preferably a saturated alicyclic group, to which a benzene ring may be fused together with CR ₅ , or a group , k represents the number 0, 1 or 2, m represents the number 1, 2, 3 or 4, n represents the number 0 or 1, R ₁ is hydrogen, C _1-4 alkyl, represents cyano, and if k is 0 also represents chlorine, bromine or iodine; R ₂ and R ₁₁ are C _1-4 mono- or polysubstituted with hydrogen, halogen, nitro, optionally fluorine or chlorine; alkyl or alkoxy,
C _3-4 alkynyloxy, amino, NH (C _1-4 alkyl), N (C _1-4 alkyl) ₂ , cyano, phenyl,
C _3-6 cycloalkyl, C _3-4 alkenyloxy, hydroxy (C _1-4 alkyl), NHCOR ₆ , CO ₂ R ₆ ,
CONR ₇ R ₈ , or C _2-8 alkyl interrupted with oxygen, or , R ₃ , R ₄ , R ₁₂ and R ₁₃ are hydrogen, halogen,
C _1-4 alkyl, C _1-4 alkoxy, (C _1-4 alkyl)
-S(O) _P (p=0, 1 or 2), represents hydroxy or (C _1-4 acyl)oxy, or R ₃ /
R ₄ and R ₁₂ /R ₁₃ both represent methylenedioxy or ethylenedioxy bonded to two adjacent atoms on the phenyl ring, R ₅ and R ₆ represent hydrogen or C _1-4 alkyl,
In addition, R ₅ can also represent a 5- to 7-membered ring, preferably a saturated alicyclic group, to which a benzene ring may be fused together with the C atom to which it is bonded and Y, and R ₇ and R ₈ are C represents _1-4 alkyl, C _3-7 cycloalkyl, phenyl, benzyl, furfuryl, tetrahydrofurfuryl or C _3-4 alkenyl,
Alternatively, R ₄ may be hydrogen, and both may be O, NR ₆
or can represent a C _3-5 alkylene chain, which may be interrupted by S(O) _q (q=0, 1 or 2), and R ₉ and R ₁₀ are both R ₇ and R ₈ of one type of chain. and represents hydrogen or C _1-4 alkyl, provided that A and B cannot simultaneously represent a group selected from the group consisting of phenyl, monohalophenyl, mononitrophenyl and monoaminophenyl. ], which is a manufacturing method of formula (a) (wherein A, B and R ₁ are the same as above). Acrylic acid or a reactive derivative thereof, optionally prepared in situ, has the formula H-Q () (wherein Q is the same as above). or (b) with an N-activated derivative of the compound of formula, optionally prepared in situ; (In the formula, A and B are the same as above.) (In the formula, R ₁ and Q are the same as above,
R and R′ are the same or different and represent a straight-chain or branched C _1-12 alkyl group, a C _7-12 aralkyl group or a C _6-10 aryl group, and the alkyl chain is interrupted by O or S. Aryl and aralkyl groups may also be mono- or polysubstituted on the nucleus by halogen, C _1-2 alkyl or alkoxy. ) or (c) a compound of the formula in which X represents oxygen is reacted with phosphorus pentasulfide in an inert solvent; or (d) a compound of the formula (wherein A, B, R and R ₁ are the same as above) is reacted with an amine of the formula, or
or (e) in the case of a compound of the formula where k represents 0, by adding chlorine, bromine or iodine to the double bond and then removing the corresponding hydrogen halide, or (f) where R ₁ represents halogen. A compound of formula X is reacted with copper cyanide () or (g) a ketone of formula In the formula, Z represents Q or OR, and Q and R
is the same as above. ) or (h) a compound of the formula in which A and/or B contain a lower to intermediate alkoxy group or a benzyloxy group is ether-cleaved and optionally the free phenolic OH group is then ether-cleaved. acylation or (i) reducing a compound of the formula in which A and/or B contains a nitro group to the corresponding amino compound, and optionally resolving the resulting cis/trans isomer mixture and/or (a) or above
The above-mentioned method is characterized in that the compound of the formula (2) having a basic group obtained in step (i) is converted into an acid addition salt.