CA1311240C

CA1311240C - Arylcarboxylic acid derivatives, the preparation and use thereof

Info

Publication number: CA1311240C
Application number: CA000545601A
Authority: CA
Inventors: Wolfgang Buck; Erich Raddatz
Original assignee: Shell Internationale Research Maatschappij BV
Current assignee: Shell Internationale Research Maatschappij BV
Priority date: 1986-08-29
Filing date: 1987-08-28
Publication date: 1992-12-08
Anticipated expiration: 2009-12-08
Also published as: PT85616A; EP0262393B1; NZ221592A; HU203320B; MY101353A; DK451887A; ES2043625T3; AU7766787A; DK174902B1; JP2632863B2; JPS63132867A; HUT48204A; CN87106006A; IL83684A0; GR3006845T3; EG18578A; JPH09118659A; EP0262393A1; BR8704461A; KR960011716B1

Abstract

Abstract Arylcarboxylic acid derivatives, the preparation and use thereof The compounds of formula

Description

~ 3 ~

M~ 52-054 Arylcarboxylic acid derivatives, the preparation and use thereof The invention relates to new composi~ions for comba~ing phytopathogenic fungi, new active substances for these compositions and processes for preparing the active substances.
According to one feature of the invention there is provided a fungicidal composition comprising a compound of formula (I) ll l2 Aryl - X - Q - CON - C - R3 (I).

~ In formula I and hereinafter-: 15 Aryl represents a phenyl group, either unsubstituted or mono- to trî-subst~tuted by Cl 5 alkyl groups, Cl 5 alkoxy groups, Cl_5 alkyl-SO~
groups wherein n represents one of the integers 0, 1 or 2, halogen atoms, groups of formula NO2, CF3, CN, CH3OCH2, ~CH3)2NCH2, COOalkyl.
CONH2 or phenyl gxoups; a 1- or 2-naphthyl group; an opt~onally chlorine-substituted ~: 2-, 3- or 4-pyridyl group; or a pyrimidyl or quinolyl group;

~:~ Q represents a group of formula - C - ~C~2)m .~ R5 wherein m is one of the integers 0, 1 and 2;
: 30 represents a hydrogen atom or a Cl_5 alkyl group or an allyl group, .;

~ 3 ~
~ 2 R2 and R3 independently represent hydrogen atoms, Cl 6 alkyl groups (which may also contain an O or S atom in the chain~, C3 7 cycloalkyL groups, phenyl groups or groups o ~ormula CH2-COO~tC1 5 alkyl); or R2 and R3 together represent a group of formula ( 2)~ r (CH2~5-. or -CH ~ (C~l2)4-;

R4 represents a group formula CN or CON~2;
represents a hydrogen atom or a group of formula CH3 or C2H5;

R6 represents a hydrogen atom or a group of ormula CH3; and X represents an oxygen or sulphur atom.

~he majori~y of compounds of formula I are new and thus according to a further feature of the . ~ invention there i5 provided compounds of formula : (I) Il l2 Aryl - X - Q - CON - C - R3 (I) ., ~4 wherein : :
: 30 Aryl represents a phenyl group, either unsubstituted or mono- to tri-substituted by Cl 5 alkyl groups, Cl_5 alkoxy groups, Cl_5 alkyl-SOn ` groups where.in n represents one of the integers : 0, 1 or 2, halogen atoms, groups of formula : 35 N02, CF3, CN, CH30CH~, tCH3)2NCH2, COOalkyl, CONH2 or phenyl groups; a 1- or 2-naphthyl group; an optionally chlorine~substituted 2-, 3- or 4-pyri.dyl group; or a pyrimidyl or quinolyl group;

Q represents a group of formula - C - ~CH2)m wherein m is one of the integers 0, 1 and 2;
Rl represents a hydrogen atom or a~ Cl_5 alkyl group or an allyl group, R2 and R3 independently represent hyclrogen atoms, Cl 6 alkyl grQups (which may aLso contain an O or S atom in the chain)~ C3 7 cycloalkyl groups, phenyl groups or groups of formula CH2-COO-(Cl_5 alkyl), or R2 and R3 together represent a group of formula (CH2)4 ~ ~(C~2)s~~ or -CH - (CH2)~-;

R4 represents a group ~ormula CN or CONH2;
R5 represents a hydrogen atom or a group of - formula CH3 or C2H5;
-R6 represents a hydrogen atom or a group of :~ 25 formula CH3; and - ~ X represents an oxygen or sulphur atom;
.
: optionally in the form of racemates or mixtures of the optical isomers or in the orm of the pure enantiomers or diastereomers, , with the proviso that ~: 35 ~a) aryl-X- does not represent J~

c~

when Q represents a group of formula ~CH(CH3) and CR2R3R4 represents a group of formula -CH2CN;

: (b) aryl-X-Q does not represent Cl Cl ~ .O-CH2-when (1) Rl represents a hydrogen atom or : a:Cl 4 alkyl group and : (2) R2 represen~s a hydrogen atom or a methyl or etbyl group and : R3 represents a hydrogen atom or a methyl, ethyl, phenyl or henzyl group or ~R2 and R3 together represent a group of-~ormula ~(CH2)4 or (CH2)5~ _ 3) R4 represents a~group:o formula CN

30: ~(c~aryl-X-Q does not represent any of the . following formulae CI CI

3 5 C l ~ O- C\I ( CH ~ C l~ O- CH ( CH

Cl Cl "

~ .

~ 3 ~ 'g ~

CF3 ~ O-CH(CH3)- or 3 ~-CH(C2H5)-when CR2R3R4 represents a group of formula C(C~3)2CN; and (d) -X-Q-CONRl-CR2R3R4 does not represent a group of formula -O-CH2-CON~-CH2CN when aryl represents CH

~ _ Cl ~ - ~ CONH

The compounds of formula I may contain asymmetric carbon atoms and the invention includes the individual ~` enantiomers of such compounds and also mixtures thereof.
If the substituents Rl to R6 contain hydrocarbon chains, these may be straight or branched and may be identical to or differ~nt from one anotherO
Chains with up to 4, more particularly up to 3 carbon atoms are preferred. The preferred alkyl substituent in the aryl group is 2 methyl group.
Halogen atoms include fluorine, chlorine, bromine and iodine, preferabIy chlorine or fluorine. The substituents in the aryl group may be identical or different although the groups of formulae CF3, CN, NO2~ (CH3)2WCH2 and C1_5 alkyl~SOn and the phenyl group generally occur only once. If aryl .

represents a quinolinyl group it is preerably an 8-quinolinyl group.

The compounds of formula (I) may be prepared by several processes and ~hese processes from a still further feature of the invention. ~hese proce~ses include:

1. reaction of a compound of formula (II) Aryl - X - Q - COY (II) .
wherein aryl, X and Q are as hereinbefore defined and Y represents a leaving group, eDg. a 15halogen atom (preferably chlorine~, or an alkoxy, hydroxy or acyl group, with a compound of formula (III) HN - C - R3 (III) wherein Rl - R4 are as hereinbefore defined, thereby eliminating ~Y; and ~ 25 : 2. reaction of a compound of formula (IV) Aryl - XM (IV~

wherein aryl and X are as hereinbefore defined and M indicates a hydrogen atom or an alkali . metal cation r with a compound of formula ~V) 1l l2 Z - Q - CON - C ~ R3 (~) , wherein Rl to R4 and Q are as hereinbefore defined and Z represents a halogen atom or an arylsulphonyloxy group.

The reaction of ~ype ~1) i5 pr,eferably carried out in an inert solvent, e.g. methyl~ene chloride, toluene, acetonitrile, an ether, or in a mixture of solvents at temperatures between ambient temperature and the boîling temperature of the reaction mixture;
the reaction will be promoted if an HY~binding agent is present, for example a base i HY represents an acid such as HCl, or dicyclohexylcarbodiimide or carbonyldiimidazole if HY represents water.
The starting materials of formula (II) are known compounds or may easily be prepared by conventional methods. Thus compounds of formula ~II) wherein Y = O~ may be obtained for example by reaction of a suitable phenol or thiophenol (aryl~XH) with an ester of a suitable bromcsubstituted carboxylic acid in the presence of a base and subse~uent hydrolysis of ~he ester~ From the carboxylic acids thus obtained, ;~ the corresponding carboxylic acid chlorides of :~ 25 formula (II) are formed, e.g. by reacting with thionyl chloride.

The a-amino acid nitriles (compounds of formula ; (II) wherein R4 = CN), may be prepared by Strecker synthesis from the corresponding ketone or aLdehyde, : NaCN and NH4Cl in water (see Houben-Weyl, Vol.
: VIII, page 274ff (1952)). The ~ amino acid amides ( compounds of formula (III) wherein R4 = CONH2) are obt~ined from the corresponding nitriles by partial hydrolysis.

- ' :
' The reaction of type (2) may be carried out in an inert polar solvent. If M = H, a base is desirably added. Conditions under which a compound of formula (IV) wherein M = K or Na is formed are preferred.

The preferred definitions of Z in formula (V) are a bromine atom or a group of formula CH3-C6H4-SO3-whilst the preferred solvent is acetonitrile.
The reaction is generally carried out at elevated temperatures, e.g. at reflux temperature. Suitable bases include, for example, alkali metal carbonates, alkali metal hydroxides, and optionally also sufficiently basic amines such as triethylamine.

Depending on the definitions of R2 to R6, compounds of formula I with one or two centres of asymmetry may occur. The isomers may, if desired~ be separated by conventional methods or synthesised directly by using optically active starting products. -20Two methods of preparing optically active compounds - of formula (II) from an optically active ~-hydroxy acid ester are illustrated below (the asymmetric carbon is marked with an asterisk~:

_ 9 _ l*3 HO C H-COOAlkyl (-) CH ~ _S2c ~ ~ P~ 3 10C 3 ~ SO2-O-C H-COOAlkylBr-C H-COOAlkyl Ar-OH ¦ Ar-OH

Ar-O-C H-COOAlkyl Ar-O-C H-COOAlkyl (~) (-) NaOH; HCl ¦ NaOH; HCl ~

~H3 CH3 ~r-O-C H-COOH Ar-O-C H-COOH
~: ( + ) , ( - ) SOC12 oder SOC12 oder Cl-CO-CO-Cl Cl-CO-CO-Cl ~: Ar- O l~H C ~ jCH3 ~O
; : 30 (-) \Cl (+) C1 , ~ ` (II), (-)-Form (II), (~)-Form ~ ~ 35 I'Alkyl~ preferably represents methyl or ethyl.
;~ Other compounds of formula (II) may be prepared according to the same general scheme.

, ~ 3 ~

Similar steps lead to optically active starting materials of formula (V); in this caser too, other optically active compounds of formula (V) may be obtained accordingly.

HO-C H-COOAlkyl C~3~S02Cl CH3 ~ SO20-C H-COOAlkyl ¦NaOH; HCl ;~ CH3 ~ SO20-C H-COOH

SOClz CH3 ~ SO20-C H-C/

3 rO~ S 2 - C ~ co NR 1- C - R 3 (V), (-)-Form The compounds of formula I have a fungitoxic effect on phytopathogenic fungi, and accordingly methods of preventing and/or combating fungal infections in plants form a yet further feature of the invention.
The compounds may be used particularly against 5 fungal diseases in rice, for instance Piricularia.

Although the new compounds are partly derived from herbicides (Dichlorprop, 2,4-DB) they are surprisingly well tolerated by plantsu To prepare the fungicidal compositions according to the invention the compounds of formula (I) are processed with conventional excipients and/or carriers to produce the usual preparations, which may be 15 diluted for use in the form of a spray liquor with suitable quantities of water. Preparations o~
this kind include, for example, emulsifiable and soluble concentrates, wettable powders, dusti~g powders and granules which may contain up to 80 20 by weight of active substance.

The activity of the compounds according to the inven~ion, e.g. against Piricularia, was tested on rice seed under tropical conditions. 2 rows 25 of rice seed (I and II) between older rows naturally infected with Piricularia were treated on the 41st, 45th and 49th day after sowing with spray liquors containing specific quantities of active substance.
A control treated only with water was used as a 30 comparison. The results were graded 6, 8, 10 and ; 13 days after the last spraying (expressed as a % o~ plants attacked)~

The compounds according to the invention proved highly effective against Piricularia and well tolerated by the plants.

Additional tests are described hereinafter.
.

.
A. Leaf treat_ent Rice plants were first grown in propagation trays.
They were sprayed until dripping wet with emulsions or suspensions containing 1000, 500 or 250 ppm of the active substance in question. Two days after treatment the propagation trays were left in the open between infected rice plants for 5-6 days to allow infection to occur. Findings were evaluated 5-8 days later.

B. Soil treatment Rice plants were first grown in flower pots. Emu:Lsions or suspensions containing 500 ppm of the active substances specified were poured onto the roots.
Two days afteL treatment the pots were left in the open for 4-6 days between rice plants infected with Piricularia in order to allow infection to occur. Tbe results were evaluated 5-7 days after the infection.

The findings were graded 1 to 3:

1: no attack 2: slight attack 3: attack similar to that of the untreated control.
The numbers given in Table A hereinafter are averages from 3 tests and several grades awarded at different ~imes.

C. Application under water (submerqed application) Rice plants were planted in earth-filled buckets.
Water was added until it formed an unbroken covering over the earth. A quantity of active substance was added in the form of a suspension or emulsion to correspond to an application of 8 or 4 or 2 kg/ha active ingredient. Two days after treatment the ~est plants were left in the open between infested rice plants and remained exposed to infection throughout the experiment. The results were evaluated one day after attack had occurred on the untreated control and the evaluation was carried out 4-5 times (3 experiments with each substance). Evaluation was as in A and B. The numbers in the table are the averages from three experiments and several grades awarded at different times as the experiment progressed.

,: ~

Table_A,Test results Active Concentration Numbe~ of attacks Test C
substance of active according substance Test A Test B Number of to [ppm] kg/ha Attacks Example:
_ _ _ Tab. II 1000 1.0 No. 62500 1.0 1~8 8 2.0 250 1.0 _ _ Example1000 1.0 4 1.8 No. 9500 1.0 2.0 2 2.2 : 25~ l.S
.
Tab. II1000 _ No. 1500 1.0 2.5 8 1.8 25~ 1.0 _ _ . _ _ Tab. V1000 1.0 No. 2500 1.5 1.0 4 1.5 250 2.5 _ , _ Example1000 1.0 8 1.8 No. 4500 1.8 2.1 250 2.1 : _.
Tab. II 1000 1.1 No. 2 500 ~ 1.0 _ 4 2.0 250 2.0 __ Tab. II 1000 1.0 No. 33 500 1.0 _ 250 2.0 ~ ~ _ ; Example 1000 1.5 No. 6e 500 2.0 2.0 . 250 2.0 _ . __ Tab. I~ 1000 ~o. 6 500 1.0 1.
250 1.0 _ ~ ~ 3~ a ~ Q

Example 1 2-(2,4-DlchlorophenoxY)~pro~ionic acid-N-(l-ethyl-l-cyanopropyl)-amide Cl ~ CH3 IC2H5 Cl ~ O - CH - CONH- C 2 5 :` lû
2.2 g of 3-amino-3-cyanopentane and 2.4 g of triethylamine are dissolved in 100 ml of methylene chloride.
5.1 9 of 2-(2,4-dichlorophenoxy)-propionic acid chloride are added and the mixture is stirred overnight at ambient temperature. The solution is extrac~ed with water and sodium hydrogen carbonate solution, dri~d and evaporated down. The residue obtai~ed ~i consists of 6.3 g (96% of theory) of a brownish viscous oil which crystallises when stirred with diisopropylether.
. ~
Yield: 4.9 g of white solids (74% of theory) Melting point: 100 - 102C

The structure is confirmed by spectroscopic investigation.

AnalySiS: C15H18C12N22 - C~ H% Cl~ N%
Found: 54.58 5.54 21.06 %.35 Calculated: 54.72 5.51 21.54 8.51 Example 2 2-(4-MethylthioPhenYloxY)-propionic acid-N~ cyano-1,2-dimethylpropyl)-amide 3 $ o - CH - CONH - C - CH
CN C~3 2.5 g of 2-bromopropionic acid-N-(l-cyano-1,2-dimethyl-propyl~-amide (prepared analogously to Example 5a) and 1.4 g of 4-methylmercaptophenol are dissolved in 50 ml of methylisobutylketone. After the addition of 1.5 g of potash the mixture is stirred for 3 hours at 80C. The solution is suction filtered : and evaporated down. 2.8 g of brownish oil are ~l obtained (91.5~) which crystallises when stirsed with diisopropylether.
M.p. 83-86C

AnalysiS: ~16 2~ 2 2 :25 C% H% N~ S~
Found: 62.48 7.24 9.23 10.34 Calcul~ted: 62.71 7.24 9.14 10.46 .
The structure was confirmed by spectroscopy.
: Exam~le 3 ~

2~ Chloro-2-methylphenoxy)-propionic acid-N-[3-cyanopent-3=yl]-amide ; 4.4 g of 2-amino-2-ethylbutyronitrile (0.039 mol) ~ and 4.6 g of triethylamine (0.046 mol) are dissolved ;
;

~ 17 -in methylene chloride, 9.0 g of 2-(4-chloro-2-methyl-phenoxy)-propionic acid chloride (0.039 mol) are added dropwise with stirring. The mixture heats up. It is stirred for a fur~her 3 hours without heating, extracted successively with water and bicarbonate solution, then dried and evaporated down. The residue obtained consists of a brown oil (10.8 g) which crystallises when stirred with isopropylether. The product is suction filtered and dried.

Yield: 10.6 g (88% of theory) of white solids M.p.: 125 - 126C.

Elemental analysis and NMR spectrum confirm the formula given.

Example 4 2-(4-Chloro-2-methylphenoxy)-propionic acid-N-[2-cyano-3-methylbut-2-~1]-amide Analogously to Example 3 the title compound is obtained from equimolar quantities of 2-amino-2,3-dimethylbutyronitrile.

Yield: 76% o theory; m.p.0 97 - 99C.
.
The product is initially obtained as a brown oil.
It consists of 4 isomers. The mixture can be resolved into 3 fractions by step-wise precipitation with cold ether.

From 11.1 g of oil are obtained:
Fraction I: 1.8 g of white solids m.p.: 117-118~C;

. r~,J ~

raction II: 1.8 g of brownish solids m.p.: 94 96C; rac~ion II~: 5.6 9 of reddish oil ~purified by chromatography3 NMR spectroscopy indicates enrichment: of the pairs of enantiomers in Fractions I and II:

Fraction I Enantiomeric pair I to enantiomeric pair II 89 : 11 (diastereomeric ratio) Fraction II Enantiomeric pair I to enantiomeric pair II 26 : 74 The pairs of enantiomers may be further concentrated by recrystallising the fractions.

:
: :

.~

rD .~ ~, The following compounds of the general formula given below were also obtained in accordance with the preceding Examples:

Rl l2 Table I

No. Q R2 R3 Rl R4 M p. [C]
. _ . . .

l CH2 ~2Hs C2H5 H CN 86-e8 2 CH(CH3) 3 7 CH3 H CON~ 108-lll 3 CH2 i 3 7 CH3 CONH2 105-107 4 CH2 i_C3H7 CH3 H CN 102-103 c~ScH3) n C3 7 CH3 H C~ 71-75 6 CH(C~3) CZH5 CH3 H CN 86-87 7 CH(CH3) 3 7 CH3 H CONH2 100-~02 3 CH(CH33 n CSH11 CH3 H CN
9 CH~CH3) (CH2~5 H CN 134-136 CH -(CH2j5 H CN 118-120 12 CH(CH3) i C3H7 CH3 CH3 CN Oil 13 CH(CH3 -(CH2)4- H CN 143-146 14 CH(CH3) -fH-(CH2)4 H CN 121-lZ7 ; C~13 Example 5 2-(4-Chlorophenylthio)-propionic acid-N-(l-ethyl-L-cyanopropyl)-amide a) 2-Bromopropionic acid-N-(l-ethyl-l-cyanopropyl)-amide \ C /CH3 o Br 36.5 g of 2-amino-2-cyano-n-pentane in 100 ml of methylene chloride are added dropwise, with stirring, over a period of 40 minutesr to 88.4 g of 2-bromopropionic acid anhydride (0.325 mol) q dissolved in 280 ml of methylene chloride.
After stirring overnight, the soLution is extracted with water and sodium bicarbonate solution, dried and evaporated down. The remaining oil : is triturated with a little ether whereupon the product crystallises out.
M.p. 85~87C
Yield: 61.2 g (76.5% of theory) b) Cl ~ S - ~HCONH - C - C H
CN

5.8 g of 4-chlorothiophenol (0.04 mol) are stirred in 150 ml of methylisobutylketone with 12.2 g of potassium carbonate at 90C for 10 minutes.
9.9 g of 2-bromopropionic acid-N-~l-ethyl-l-j h'~

cyanopropyl)-amide are added to the resulting suspension with stirring and the mixture is stirred Eor another 5 hours at about 90C.
rhe solution is filtered, extracted successively with water, 2N sodium hydroxide soLution and water, dried with magnesium sulphate and evaporated down. A brown oil i5 obtained wh:ich hardens to form a bro~nish crystalline mass when stirred with a little ether.
M.p. lQ8-110C
Yield: 7.2 g (58.1~ of theory) Elemental analysis C H N Cl S
Calc.: 57.96~ 6.16% 9.01~ 11.4% 10.32%
Found: 57.77% 6.35% 8.86% 11.32% 10.28%

The following compound is also obtained according to the preceding Example CH~
Cl ~ S - CHCO~H ~ 0 ~ CH(CH3)2 M.p.: 106-109C.

Example 6 ; 30~ 2-~4-Chloro-2-methylphenoxy)-pro~_onic acid-N-(l-ethyl-l-cyanopropyl)-amide a~ Methyl (-)-0-(4-methylphenylsulphonyl)-lactate 26.9 g of triethylamine are added dropwise to a solution of 25.2 g of methyl S-(-)-lactate and 46.1 g of p-toluenesulphonic acid chloride 2'~

in 160 ml of toluene. The mixture is stirred overnight and the precipitate is removed by suction filtering~ The toluene solution is extracted with dilute hydrochloric acid and water, dried with sodium sulphate and evaporated down. 55.9 g of colourless oil are obtained, which is purified by vacuum distillation.
B~p~o 2: 148-152C [~]24: ~50.1~ (ethanol) Yield: 43.5 g (70% of theory) b) Methyl (~)-(4-chloro-2-methylphenoxy)-propionate 41.9 g of methyl S-(-)-0-(4-methylsulphonyl)-lactate and 23.1 g of 4-chloro-2-methylphenol are dissolved in 100 ml of acetonitrile, 50 g of potash are added and the mixture is refluxed for 10 hours with stirring. The solution is suction filtered and evaporated down. The residue is taken up in toluene, extracted with lN eodium hydroxide solution, dried and concentrated by evaporation. 32.2 g of reddish liquid are obtained (87% of theory) c) (+)-4-Chloro-2-methylphenoxypropionic acid ~he crude product obtained in b) (32~2 g) is dissolved in~l00 ml of acetone. A solution of 6.8 g of NaO~ in 30 ml of water is added ; dropwise with stirring and while cooling with ice. After stirring overnight the mixture is diluted with water and extracted with methylene chloride. The aqueous solution is acidified with conc. hydrochloric acid and the product precipitated is extracted with methylene chloride.
The methylene chloride solution is separated off, dried and evaporated down. An oily residue is obtained which solidifies immediately.

M.p.: 62-72C Ipressed onto clay) [a]24: + 14.1 tethanol) Yield: 27.7 g (91% of theory) d) ~ 4-Chloro-2-methylphenoxypropionic acid chloride 27.2 g of (~)-4-chloro-2-methylph~enoxypropionic acid and 30.2 g of thionyl chloride are stirred with 100 ml of toluene for 3 hours at 100C.
The solution is evaporated down in vacuo. 29.6 g of brown oil are obtained, which is reacted without purification.

e) (+)-2-(4-Chloro-2 methylphenoxy)-propionic acid N-tl-ethyl-l-cyanopropyl)-amide 8.4 g of the crude product from d) are added dropwise to 4 g of 3-amino-3-cyano-n-pentane and 4O4 9 of triethylamine, dissolved in 100 ml of toluen , at -20 ~o -30C with stirring.
~he mixture is then stirred for 3 hours at RT, extracted with water and the solution is evaporated down. The oily residue (8.8 9) is stirred with diisopropylether, whereupon a crystalline product - 25 is precipitated and then separated off.
Yield: 2.8 g (25% of theory~
M.p.: 98-100C
: [a]22: + 9.1 (ethanol~
:: :

::

~ .

_a~E~

~? -2-(4-Chloro-2-methylylphenoxy)-propionic acid-N (l-eth l-l-c ano ro l)-amide y y P Py .
a) Ethyl (+)-2-bromopropionate 47.2 9 of ethyl 5-(-3-lactate are dissolved in 300 ml of methylene chloride. 108 g of phosphorus tribromide are added dropwise~ The reaction is exothermic. After s~irring overnight at RT the mixture is poured onto ice and stirred with waterO The methylene chloride solution is extracted with bicarbonate solution, dried and evaporated down. The residue is distilled.
Yield: 33.8 g; colourless oil (47% of theory) BP25 mbar b) Ethyl ~ (4~chloro-2-methylphenoxy)-propionate The product described in a) (33.8 g) is dissolved together with 26.7 g of 4-chloro-2-methylphenol in 300 ml of toluene and after the addition of 52 g of K2CO3 it is refluxed for 10 hours with stirring. The solu~ion is suction filtered, extracted twice with lN sodium hydroxide solution, dried and evaporated down. 34.3 g of clear liquid are obtained ~76% of theory) [ ~22 -14 46 (ethanol) c) (-~-(4-Chloro-2-methylphenoxy)-propionic acid ; ((-)-CMPPj Hydrolysis of the ester obtained in b) is carried out as in Example 6c).
From 24.2 g of ethyl ~ (4-chloro-2-methylphenoxy)-propionate, 19.7 g of (-)-(4-chloro-2-methylphenoxy)-propionic acid are obtained (92% of theory).

2 ~

M.p.: 69-75C
L~]22 _9 679 (ethanol) d) (~)-(4-Chloro 2-methylphenoxy)-propionic acid chloride (~+)-CMPP-chloride) The acid described in 7c) is converted analogously to Example 6d~ into the acid chloride which is further processed without purification.
From 8.6 g of (-)-CMPP~ 8.4 9 of l+)-CMPP chloride is obtained as a brownish oil (90% of theory) [~]22: +4.4B6 (CCl4) e) (-)-2-(4-Chloro-2-methylphenoxy)-propionic acid-N-(l-ethyl-l-cyanopropyl)-amide The (~)-CMPP chloride is reacted with 3-amino-3-cyano-n-pentane as described in Example 6e).
3 g of (-)~2-~4-chloro-2-methylphenoxy)-propionic acid-N-(l~ethyl-l-cyanopropyl)-amide are obtained t28~ of theory) from 8 g of (*)-CMPP chloride.
M.p.: 98-100C
[a]D : -8.584 (ethanol) :
A variant for the preparation of the dextrorotatory phenoxypropionic acid amides is described hereinafter taking as an example (+)-2-(4-chloro-2-methylphenoxy)-propionic acid-N-(l-ethyl-l-cyanopropyl)-amide:
:
Example 8 (+~-2-(4-Chloro-2-methyl~henoxy)-propionic acid-N-!l-ethyl-l-cyanopropyl)-amide : 35 a) t~)-0-(4-Methylphenylsulphonyl)-lactic acid chloride .

~ 3 ~

17.9 g of (-)-0-(4-methylphenylsulphonyl)-lactic acid (Helv. Chim. Acta 65/1240 (1982)) and 13 g of thionyl chloride are stirred at 95-100C
for 3 hours. The product is evaporated down in vacuo and degassed. 19.2 g of brown oil are obtained (100% of theory)~

b) (-)-0-(4~Methylsulphonyl)-lactic acid-N-~l~ethyl-l-cyanopropyl)-amide 18.8 g of the crude product from 8a) are added dropwise at -20 to -30C to a solution of 3 g of 3-amino-3-cyano-n-pentane and 8.8 g of triethyl-amine in 200 ml of toluene. The mixture is stirred for 3 hours at -20C and then overnight at RT. The solution is extracted with water and evaporated down. 23.4 g of brown clear oil are obtained (96% of theory~ which is crystallised by stirring with diisopropylether.
M.p.: 57-60C [a]D -40.4 (ethanol) Yield- 8.4 g (34~ of thevry) c) (+)-2-(4-Chloro-2-methylphenoxy)-propionic acid-N-(l-ethyl-l-cyanopropyl)-amide 4.7 g of (-)-0-(4-methylsulphonyl)-lactic acid N~ ethyl-l-cyanopropyl)-amide and 2 g of 4-chloro-2-methylphenol are dissolved in 100 ml of toluene. 4.5 g o powdered potash are added and ~he mix~ure is refluxed for 12 hours with stirring. The solution is suction filtered, ; ; extracted with lN sodium hydroxide solution and evaporated down. 3.1 g of yellow oil are obtained (72% of theory) which crystallises ~; 35 when stirred with diisopropylether. 2.2 9 of white crystalline solids are obtained t51~ of theory).
M.p.: 97-99C [a]D : +11.94 (ethanol) ~3 ~

In accordance with Examples 6 to 8, the dextro-and levorotatory enantiQmerS of the following compound are also prepared:

c~3 ~ CH3 IH3 CL_( O ~-O - CHCONH - C - CH(CH3)2 ,J CN

Example 9: [a]22 = 9.1 (ethanol) oils, mixtures of diastereomers ~xample 10: [a]D - -7.65 (ethanol) The following compounds, listed in Tables II to IX, were prepared by analagous methods.

o o oo ~o ~ X ~ X

~ , .
S X

, ~- ~, ~ ~ C ~ ,z :~:
: , ~ ~C

:: ' : ~

~: o . o ~ ~
: ~ ' o _ I ~
Z I

.. . .

.
' :, ~' ' . ::
.

~q ~

C~ ~ ~ ~
~_ t~
_. o ,_ ~ o o ~

~ ~ ~ ~ ~ r- ~
~ :~: x ~ x n; :~: S

' Z Z Z Z Z Z ' :1:

_~ _~ X
C,~ . o S ~ X
, ( :
C~
~ ~ _ ~ ~ ~ , C~
~: ~ ~ C~
~ ~ X ~ _ :
: :: .
2 --r T S T T T

~ ` ~ ' :: _ :~
,~ ~
O '~ ~ a~ o ~

~ 3 . L ~

~
~ 9 l I
r o o ~: ~ O :

X3~

~;~ Z ;r: ~ Z Z ~ Z

.~
V ~ X ~ =

: , ::
' ~ _~ .
:~:
C.~
:

~ ~ J 2 ~

~: : : ;

: : : : : :
~-: _ ~ .o r~ O ~

31 11~ L2~JL~

O _ ~ 1 ~: a~ O ~ ~

~0 S S~ S~ 1 ~ C ~ X~ X

X ~ X 2 .
~s~ æ ~ ~ z x C~l ~ C~l ~ X C~ V
" 3 '~ c ~, ~, 8-:

; ::

X ~ 2 ~ S

; X 2 .

3 2 ~ 3 - L 2 ~ ~
-~, , o --, ~ ~ o Cl4 !Ir ~ ~ O ~r X ~ o ~
~O
C~

C~3~ ~ :Z 2 Z C_7 . .

:1:~ X ~ , V ', C ~ C ~ S
:
.,`., : :
:~ : ::
C~ S~ ~ ~ S~

:
~: T ~ :C --. ~ ~ .

L. _ ~ _ ~: ~ C~
.~

: , :

- 33 'D3~J~2~` a o ~ ~ o .- ~ ~

~; C~ X X :~ X X

~ :~ - s ;~: Z Zo X C~ Z

C~
^
C~
Rl~ C~ X S C C,> C
~ ~ .

::
~:

: : : :

:: ~ ~

~, ,~ ~ ,_ . ~ C~ o ~: ~ ~ "~

3a û O ~; O o _ I O N
O

C" C~
~;

~' :~: X X ~ ~ X S

:~:
~ z ~, oZ a: z z ~

' C~
2 ~

:
::
_~

': :
~ , ~ ~ V

: ~ ~ O
Q ~
~ q ~ .

~ 3 ~

o ~ ~ ~ ~ ~ ~ _~
~r: V ~ c~ r;_~

~ C~ 2 .

~ _ _ _ _ _ a~ :~:~ x~ =~
~ _ _ :S: _ _ _ _ ~: : : :
~ .

:::
::
U~
X
~ : 5: S Q = `
:: ~ :

X '~ 2 :~ ~ X I ~ r ~: O ~ O

, .. . . .

2 ~
3~;

o V~
, , CO
, ~ ~
a. o o ~ o c~, o~

X 1 ~ ~ ~

:~: 8 X :~ S 3:. :
., lY~ ~, 3 Z z . .

. ~ ~ S , _~
C~ ~ X 3 S 3 X
X ~, g ~ ~
:~ : ~: :
~:
:
, ,'' ~ ~ ~ ~ ,.~
~ S, ::

~X S
'`.

2 ~ ~ , ~ ~ .f` ~ `O

.

37 ~3~
CO o o ~ ~ ~
~ , , .
C~` ~ o Cl~ ~ ~

:~ ~ 2~t C 2 Z :2:
1~
.

N

C~ t~ ~ N
N/ I ~ o ~t ~ C t N c~_ ~ S

~'"' :

~ '.

L. _ ,_ -C ~ ~
O
~: ~ O ~ V

~ 3 ~

T A B L E I I I
.

Compounds of formula R ' CH
R ~>_O - tC~ ) - CoNH - 0 - R
CN

No. R3 R R' Mp. (C) ---- . --.
CH(CH3 ) 2 Cl CH3 . Oi 1 } : :
` ~ 2 5 }1 Cl CH3 Oil ~:: 3 CH(CH~)z ~3 Cl :, ::
4 ~n~cSHl CH3 Cl ~: `

:

; ~ ~

, .

, : ` `' ' ` ' `': ' ' , . .

~.?~

Table IV

Compounds of formula Cl ~ 0 - CU - C0 - NU - C - R

N~ R2 R3 M p~tC]
.. ~, .....

3 C2H5 C2H5 125.126 4 CH3 CH2CH(CH3)2 1~,1-102 ~; - 5 CH3 CH20CH3 Oil 6 H CH(CN3)2 86~

7: CH3 CH2CH2CH(CH3)2 9Z-94 8 ~2H5 CH2CHtCH3)2 ~8-70 CH(CH3)2 CHtcH3)2 lO6-log 12 CH3 -CH-CH lZ7-129 ~: SCH
: 3 : 13 CH3 CH3 lZ8-130 14 CH3; ~ C(CH3)3 110-115 H C~2H5 64-66 : 16 H CH3CH2CH3 66-70 ;. 17 CH3 C6H5 148-l52 ~ CH3 CH2SC2H5 ~ 78-82 '~
; .

: :~

~ J~ L ~ ~

Table V

Compounds of f ormu 1 a CIH3 C,H3 Aryl - O - CH - CO - NH - C - R3 CN

. No. Aryl R3 M p. tC]
.

CH3 ~ CH(CH3)Z 33-66 2(~ CH(CH3 ) 2 74-76 . CN

3~ _ CH(CU3)z 71-75 , ~ ~ F
:~:

4CH300C ~ ~ CH(CH3)z 110-115 ;.
' ~.~ 5 Cl ~ CH3 l34- l37 cl .

.
~ 3 ~ 2 '~ ~

No.Aryl R3 M e toc]

3~ CH(CH3~2 80-82 '.:
7 ~ CH(CH3)2 74-76 8 Cl~ CH(CH3 ) 2 134-136 ' .

,J N
9 ~ CH~CH3)2 101-105 N_~ CH ( CH 3 ~ 2 9 4 - 9 9 Cl I IC, 1 ~ C( CH3 ~3 126- 130 : \
Cl No. Aryl E~3 M p. [C]
A

12 i)-- CH(C~5332 85-88 N
13 CO)-- CH(CH3 ) 2 170-174 N
A

14 ~~~0)-- C6H~ 129-145 ~, . ~:
C l:

~ 02N ~ ~ ~ FH ( CH 3 ) 2 C L

: : , .
~ 16 o N _~0~ CH~CH3)2 124-l26 C~l3 :
CH
~3 /
17 (0~ CH(CH~ ) 2 102-104 : ~: t ~ ~ ~ : N0 2 ' :

.. . .

',3 4~

N- Aryl R3 Mp. t C]

18 ((~ n~C3H;~ CHtCH3)2 78-80 ~ 19 CH3 ~ CH(CH3 ) 2 87-92 O2N ~ CH(CH3)2 110-112 : 21 Cll~ CH2SC2H5 Oil Cl ' 2 2 C l ~ f rom 11 2 Z3 Cll~_ ~ from l l 2 : Cl No. Aryl R3 M p. [C]
,, _ C~

24 Cl CH(C113)2 69-71 ~.
.

'; ~;

.
;' ' :

; :
: :
~ :

~' .

1 3 ~

Tab 1 e VI

Compounds of formula tCH3 tC2H5 Acyl - O - CH - CO - NH - C - C2H5 CN

N- Acyl ~ptC]
-C~ ~ 100-10:Z

2 ~r Oil N

3 tcH3~ 93-94 :

4 ~) 64-66 ~ ~ C~3 , :

(~ 92-93 LN
6 (~ t3 t3 - 9 n ~3~ 2l~
.~ 46 No. Aryl ~p[ ~C]

N
7 (~ ~84-87 8 1 _ ~OJ l Z 9 -13 1 9 OzN_(~ 117-120 0 2 ~ 1 17--1 1 8 CH
'3 ~: ~ ~N2 :: NO 2 ;~ ~: , I
1 2 CH 3 ~_ 1 2 0 - 1 2 2 1 3 02N /~_ 1 08 - 1 10 14 n~C3H7~ 71 7S
:: ~

Table VII

Compounds o f f o rmu 1 a 1 3 t 3 . No. Aryl R~ Mp. tC]

Cl ~ n~C3E17 100-102 CH3 - `

Z Cl ~) n-C3E{7 10B-111 3 (O~_ n-C3H7 111-113 ~_ N

N _ 4 (~ n-C3H7 115-117 Cl :: ~

Table VIII

Compounds o f f ormu 1 a ~ 1 ~ 2 Aryl - O - CH2 - CO - N - C - R3 CN

N o.Aryl R1 R2 R3 M P. ~ C]
~' :

Cl ~ H CH3 CH(CH3 ) 2 100-103 C1~ ~ C2U5 C2H5 86-88 3 Cl~ CH3 C2H5 CH(CH3)2 Oil r~
4 Cl_1~ H C2~5 C2H5 so_s z : '' :
S Cl ~ H CH3 n-C5H I l Oi l Table X

Other compounds according to the invention CH
Cl~o-cH?-co-NH-c-cH(c~3 ) 2 \~/ CoNH2 M p. 105-107C
. CH3 2Cl~ CH3C~3 ~H3 Oil CN
~: : CH3 3 C l ~ o- cH - co- NH- c - c 2 H s: M p ~ 6 1- 6 3 C
:~ C~l Cl `

4 ~Cl~ .O-CH-CO-NH-C-n-C3H7 Mp.70-74C
CN
: ~ Cl ' :

d ~

Examples of formulations:

Example I

Preparation of an emulsifiable concemtrate 5~0 parts by weight of active substance according to the invention 3.4 parts by weight of epoxidised vegetable oil 13.4 parts by weigh~ of a combined emulsifier of fatty alcohol polyglycol-ether and calcium alkylaryl-sulphonate 40.0 parts by weight of dimethylformamide 38.2 parts by weight of xylene The components are mixed together and, for application, dilu~ed with water to give a t concen~ration of active substance of 0.~1 : 20 to 0.1~ ~y weigh~.

Example II
Preparation of a wettable powder 10 parts by weight of active substance according to the invention 3 parts by weight of sodium fatty alcohol sulphonate 5 par~s by weight of salts of naphthalene : sulphonic acid-for~aldehyde ; condensate 82 parts by weight of kaolin .

Claims

1. A method of preventing or combating Piri-cularia in rice plants which comprises the appli-cation to said plant of one or more compounds of formula (I) (I) in which Aryl. represents a phenyl group, either unsubstituted or mono- to tri-substituted by C1-5 alkyl groups, C1-5 alkoxy groups, C1-5 alkyl-SOn groups wherein n represents one of the integers 0, 1 or 2, halogen atoms, groups of formula NO2, CF3, CN, CH3OCH2, (CH3)2NCH2, COOalkyl, CONH2 or phenyl groups; a 1- or 2-naphthyl group; an optionally chlorine-substituted 2-, 3- or 4-pyridyl group; or a pyrimidyl or quinolyl group; R1 represents a hydrogen atom or a C1-5 alkyl group or an allyl group; R2 and R3 independently represent hydrogen atoms, C1-6 alkyl.
groups (which may also contain an O or S atom in the chain), C3-7 cycloalkyl groups, phenyl groups or groups of formula CH2-COO-(C1-5 alkyl); or R2 and R3 together represent a group of formula R4 represents a group of formula CN or CONH2; X
represents an oxygen or sulphur atom; and Q repre-sents a group of formula:

wherein m is one of the integers 0, 1 and 2; R5 represents a hydrogen atom or a group of formula CH3 or C2H5; R6 represents a hydrogen atom or a group of formula CH3; optionally in the form of racemates or mixtures of the optical isomers or in the form of the pure enantiomers of diastereoemers.

2. A compound of formula (Ia):

(Ia) wherein Aryl represents a phenyl group, unsubstituted or mono- to tri-substituted by C1-5 alkyl groups, C1-5 alkoxy groups, C1-5 alkyl-SOn groups wherein n represents one of the integers 0, 1 or 2, halogen atoms, groups of formula NO2, CF3, CN, CH3OCH2, (CH3)2NCH2, COOalkyl, CONH2 or phenyl groups; a 1- or 2-naphthyl group; an optionally chlorine-substituted 2-, 3- or 4-pyridyl group; or a pyrimidyl or quinolyl group; Q represents a group of formula wherein m is one of the integers 0, 1 and 2; R5 represents a hydrogen atom or a group of formula CH3 or C2H5; R6 represents a hydrogen atom or a group of formula CH3; and X represents an oxygen or sulphur atom; optionally in the form of racemates or mixtures of the optical isomers or in the form of the pure enantiomers or diastereomers.

3. A compound as claimed in claim 2, wherein Aryl is a 4-chlorophenyl, 4-chloro-2-methylphenyl or 2,4-, 3,4- or 3,5-dichlorophenyl group.

4. A compound as claimed in claim 2 or 3, wherein Q represents an oxygen atom.

5. A compound as claimed in claim 2 or 3, wherein Q represents a group of formula CH(CH3).

6. A compound as claimed in claim 4, wherein Q
represents a group of formula CH(CH3).

7. 2-(4-Chloro-2-methylphenoxy)-propionic acid-N-[2-cyano-3-methylbut-2-yl) amide.

8. A fungicidal composition comprising a compound of formula (I), as defined in claim 2, 3, 6 or 7, optionally in the form of racemates or mixtures of the optical isomers or in the form of the pure enantiomers or diastereomers, together with excipients and/or carriers.

9. A fungicidal composition comprising a compound of formula (I), as claimed in claim 4, optionally in the form of racemates or mixtures of the optical isomers or in the form of the pure enantiomers or diastereomers, together with excipients and/or carriers.

10. A fungicidal composition comprising a compound of formula (I), as claimed in claim 5, optionally in the form of racemates or mixtures of the optical isomers or in the form of the pure enantiomers or diastereomers, together with excipients and/or carriers.

11. A process for preparing compounds of formula (I), as defined in claim 2, 3, 6 or 7, wherein (a) A compound of formula (II) Aryl - X - Q - COY (II) wherein Aryl, X and Q are as defined in claim 2, and Y represents a leaving group, is reacted with a compound of formula (III) (III) or (b) a compound of formula (V):

Aryl - X - M (IV) wherein Aryl and X are as defined in claim 2, and M
represents a hydrogen atom or an alkali metal cation, is reacted with a compound of formula (V) (V) wherein Q is as defined in claim 2 and z represents a halogen atom or an arylsulphonyloxy group, and, if desired, mixtures of enantiomers obtained are separated by conventional methods into the individual enantiomers or into pairs of diastereomers.

12. A process for the preparation of a fungi-cidal composition as defined in claim 8, which comprises admixing one or more compounds of said formula (I), as defined in claim 3, with a carrier and/or excipient.

13. A compound of formula (Ia):

(Ia) wherein Aryl represents a phenyl group, unsubstituted or mono- to tri-substituted by C1-5 alkyl groups, C1-5 alkoxy groups, C1-5 alkyl-SOn groups wherein n represents one of the integers 0, 1 or 2, halogen atoms, groups of formula NO2, CF3, CN, CH3OCH2, (CH3)2NCH2, COOalkyl, CONH2 or phenyl groups; a 1- or 2-naphthyl group; an optionally chlorine-substituted 2-, 3- or 4-pyridyl group; or a pyrimidyl or quinolyl group; Q represents a group of formula wherein m is one of the integers 0, 1 and 2; R5 represents a hydrogen atom or a group of formula CH3 or C2H5; R6 represents a hydrogen atom or a group of formula CH3; and X represents an oxygen or sulphur atom; optionally in the form of racemates or mixtures of the optical isomers or in the form of the pure enantiomers or diastereomers, for use in preventing or combatting fungal infections in plants.

14. A compound of claim 13, wherein Aryl is a 4-chlorophenyl, 4-chloro-2-methylphenyl or 2,4-, 3,4-or 3,5-dichlorophenyl group, for use in preventing or combatting fungal infections in plants.

15. A compound of claim 13, wherein X repre-sents an oxygen atom for use in combatting fungal infections in plants.

16. A compound of claim 14, wherein X repre-sents an oxygen atom for use in combatting fungal infections in plants.

17. A compound of claim 13, wherein Q repre-sents a group of formula CH(CH3) for use in combatting fungal infections in plants.

18. A compound of claim 14, wherein Q repre-sents a group of formula CH(CH3) for use in combatting fungal infections in plants.

19. A compound of claim 15 or 16, wherein Q
represents a group of formula CH(CH3) for use in combatting fungal infections in plants.

20. 2-(4-Chloro-2-methylphenoxy)-propionic acid N-[2-cyano-3-methylbut-2-yl)-amide for use in combatting fungal infections in plants.

21. A compound of claim 13, 14, 15, 16, 17, 18 or 20, for use in preventing or combatting Piricularia in rice plants.

22. A compound of claim 19, for use in prevent-ing or combatting Piricularia in rice plants.

23. A method of claim 1, wherein said compound of formula (I) is a compound of formula (Ia), as defined in claim 2.

24. A method of claim 23, wherein Aryl is a 4-chlorophenyl, 4-chloro-2-methylphenyl or 2,4-, 3,4-or 3,5-dichlorophenyl group.

25. A method of claim 23, wherein X is an oxygen atom.

26. A method of claim 23, wherein Q is a group of formula CH(CH3).

27. A method of claim 24, wherein X is an oxygen atom.

28. A method of claim 24, wherein Q is a group of formula CH(CH3).

29. A method of claim 25 or 27, wherein Q is a group of formula CH(CH3).

30. A method of claim 1, wherein said compound of formula (I) is 2-(4-Chloro-2-methylphenoxy)-propionic acid-N-[2-cyano-3-methylbut-2-yl)amide.
#8 02/12/92