AP496A

AP496A - Fungicidal 2-imidazolin-5-one and 2-imidazoline-5-thione derivatives.

Info

Publication number: AP496A
Application number: APAP/P/1993/000544A
Authority: AP
Inventors: Jean-Philippe Bascou; Guy Lacroix; Joseph Perez; Christian Schmitz
Original assignee: Rhone Poulenc Agrochimie
Priority date: 1992-07-02
Filing date: 1993-07-01
Publication date: 1996-05-28
Also published as: JPH07508528A; FR2693192A1; FI950013A0; HU9500003D0; HRP931012A2; IL106161A0; HUT69053A; TW234076B; BR9306785A; KR950702189A; FI950013A; ZA934706B; EG19984A; FR2693192B1; MX9303903A; CZ281956B6; BG99369A; WO1994001410A1; SK161494A3; AU4504593A

Abstract

1)2-imidazolin-5-one or 2-imidazoline-5-thione derivatives; 2)they are of general formula (i): in which w is sulphur or oxygen atom or an s=o group -n = 0 or 1 -a represents nr5 or 0 or s or cr5r6 or s02 or c =0 -r1 to r4 represent a hydrogen atom or an optionally substituted hydrocarbon radical, especially by halogen atoms. 30 use as fungicides in agriculture.

Description

FUNGICIDAL 2-IMIDAZOLIN-5-ONE AND

2-IMIDAZOLINE-5-THIONE DERIVATIVES

The present invention relates to new imidazolinone or imidazolinethione compounds for use in plant protection. It also relates to the processes for the preparation of the said compounds and to the products which can optionally be used as intermediates in the preparation processes. It then relates to the use of these compounds as fungicides, to the fungicidal compositions based on these compounds and to the processes for combating fungal diseases of crops using these compounds.

The present invention seeks to provide compounds which have improved properties in the treatment of fungal diseases.

The present invention also seeks to provide compounds which have a use spectrum, in the field of fungal diseases, which is improved.

The products of the invention, which possess fungicidal activity, are 2-imidazolin-5-one or

2-imidazoline-5-thione derivatives of general formula (I)

...

AP/P/ 9 3 / 0 0 5 4 4 in which:

- W is a sulphur or oxygen atom or an S=0 group

- n = 0 or 1

- A represents NR_S or 0 or S or CRsRg or S0₂ or C=0.

- R_x and R₂, which are identical or different, represent:

- H, provided that one of the 2 groups is different from H, or

- an alkyl or haloalkyl radical containing 1 to 6 10 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl, monoalkylaminoalkyl, alkenyl or alkynyl radical containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl or cycloalkyl radical 15 containing 3 to 7 carbon atoms or

- an aryl radical comprising phenyl, naphthyl, thienyl, furyl, pyridyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl, or methylenedioxyphenyl, optionally substituted by 1 to 3 groups chosen from R, or

- an arylalkyl, aryloxyalkyl, arylthioalkyl or arylsulphonylalkyl radical, the terms aryl and alkyl having the definitions given above or

- R_x and R₂ can form, with the carbon to which they 25 are bonded on the ring, a carbocycle or a heterocycle having from 5 to 7 atoms, it being possible for these rings to be fused to a phenyl, optionally substituted by 1 to 3 groups chosen from R,;

AP/P/ 93/00544

AP.004₉g

- R₃ represents:

- a hydrogen atom or an alkyl group containing 1 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl, alkylsulphonyl5 alkyl, haloalkyl, cyanoalkyl, thiocyanatoalkyl, oxoalkyl, alkenyl or alkynyl group containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl, alkoxycarbonylalkyl or N-alkylcarbamoylalkyl group containing 3 to 6 carbon atoms or

- an Ν,Ν-dialkylcarbamoylalkyl group containing 4 to 8 carbon atoms;

- R₄ represents:

- a hydrogen atom when n is equal to 1 or

- an alkyl group containing 1 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl, haloalkyl, cyanoalkyl, thiocyanatoalkyl, alkenyl or alkynyl group containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl, alkoxycarbonylalkyl or 20 N-alkylcarbamoylalkyl group containing 3 to 6 carbon atoms or

- an Ν,Ν-dialkylcarbamoylalkyl group containing 4 to 8 carbon atoms or

- an aryl radical, comprising phenyl, naphthyl, thienyl, furyl, pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, pyrimidyl, pyridazinyl, pyrazinyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl or methylenedioxyphenyl, optionally substituted by 1 to 3

AP/P/ 9 3 / 0 0 5 4 4

groups chosen from R₇ or

- an amino group disubstituted by 2 identical or different groups chosen from:

- an alkyl radical containing 1 to 6 carbon atoms

- an alkoxyalkyl, alkenyl or alkynyl radical 10 containing 3 to 6 carbon atoms

- a cycloalkyl radical containing 3 to 7 carbon atoms

- an arylalkyl, such as defined above, phenyl or naphthyl radical, optionally substituted by 1 to 3 groups chosen from R₇ or

- a thienylmethyl or furfuryl radical

- a pyrrolidino, piperidino, morpholino or piperazino group, optionally substituted by alkyl containing 1 to 3 carbon atoms;

- R_s represents:

- H, except when R« is H, or

- an alkyl, haloalkyl, alkylsulphonyl or haloalkylsulphonyl radical containing 1 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl, acyl, alkenyl, alkynyl, haloacyl, alkoxycarbonyl, haloalkoxycarbonyl, alkoxyalkylsulphonyl or cyanoalkylsulphonyl radical containing 2 to 6 carbon atoms or

AP/P/ 9 3 / 0 0 5 4 4

AP.00496

- an alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl or cyanoalkoxycarbonyl radical containing 3 to 6 carbon atoms or

- a formyl radical or

-a cycloalkyl, alkoxyacyl, alkylthioacyl, cyanoacyl, alkenylcarbonyl or alkynylcarbonyl radical containing 3 to 6 carbon atoms or

- a cycloalkylcarbonyl radical containing 4 to 8 carbon atoms or

- a phenyl; arylalkylcarbonyl, especially phenylacetyl and phenylpropionyl; arylcarbonyl, especially benzoyl, optionally substituted by 1 to 3 groups from R₇; thienylcarbonyl; furylcarbonyl; pyridylcarbonyl; benzyloxycarbonyl; furfuryloxycarbonyl; tetrahydro15 furfuryloxycarbonyl; thienylmethoxycarbonyl; pyridylmethoxycarbonyl; phenoxycarbonyl or (phenylthio)carbonyl, the phenyl being itself optionally substituted by 1 to 3 groups from R₇; (alkylthio)carbonyl; (haloalkylthio)carbonyl;

(alkoxyalkylthio)carbonyl; (cyanoalkylthio)carbonyl; (benzylthio)carbonyl; (furfury 1thio)carbonyl; (tetrahydrofurfurylthio)carbonyl; (thienylmethylthio)carbonyl; (pyridylmethylthio)carbonyl; or arylsulphonyl radical or

- a carbamoyl or thiocarbamoyl radical, optionally mono- or disubstituted by

- an alkyl or haloalkyl group containing 1 to 6 carbon atoms or

AP/P/ 9 3 / 0 0 5 4 4

- a cycloalkyl, alkenyl or alkynyl group containing 3 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl or cyanoalkyl group containing 2 to 6 carbon atoms or . - a phenyl, optionally substituted by 1 to 3

R, groups;

- a sulphamoyl group/ optionally mono- or disubstituted by

- an alkyl or haloalkyl group containing 1 to

C 10 6 carbon atoms or

- a cycloalkyl, alkenyl or alkynyl group containing 3 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl or cyanoalkyl group containing 2 to 6 carbon atoms or

- a phenyl, optionally substituted by 1 to 3

R₇ groups;

- an alkylthioalkylsulphonyl group containing 3 to

C θ carbon atoms or a cycloalkylsulphonyl group containing 3 to 7 carbon atoms;

- R₆ represents:

- a hydrogen atom or

- a cyano group or

- an alkyl group containing 1 to 6 carbon atoms or a cycloalkyl group containing 3 to 7 carbon atoms or

- an acyl or alkoxycarbonyl group containing 2 to carbon atoms or

- a benzoyl group, optionally substituted by 1 to 3 R₇ groups;

AP/P/ 9 3 / 0 0 5 4 4

AP.00496

- R₇ represents:

- a halogen atom or

- an alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio or alkylsulphonyl radical containing 1 to 6 carbon atoms or

- a cycloalkyl, halocycloalkyl, alkenyloxy, alkynyloxy, alkenylthio or alkynylthio radical containing 3 to 6 carbon atoms or

- a nitro or cyano group or

- an amino radical, optionally mono- or disubstituted by an alkyl or acyl radical containing 1 to 6 carbon atoms or an alkoxycarbonyl radical containing 2 to 6 carbon atoms

- a phenyl, phenoxy or pyridyloxy radical, these radicals optionally being substituted;

their salts and the optically active isomers.

The invention provides fungicidal compositions containing such compounds and a method for the treatment of crops using them. The invention also provides the compounds of formula I per se with the provisos that : when n = O, R« is other than an optically active residue, deriving from an optically active primary amine; when n = 1 and A is S0₂, one of the two groups R_x and R₂ must be an aryl radical; and when n = 1, A-R₄ is other than an optically active residue, deriving from an optically active primary amine or from an optically active amino acid.

Certain compounds belonging to the family of the 2-imidazolin-5-ones of general formulae:

R.

AP/P/ 9 3 / 0 0 5 4 4 ct

BAD ORIGINAL are known for their herbicidal properties by the documents of European Patents 41,623, 41,624,

215,738, 226,947, 261,705, 303,863, 433,655 and 436,483 and Patents US 4,925,944, DE 3,913,757, GB 2,167,062,

GB 2,192,877 and JP 3,196,570.

The imidazolinones of formula:

AP/P/ 9 3 / 0 0 5 4 4 have been described for their pharmaceutical properties by Applications WO 9,114,679, JP 8,055,467 and DE 1,176,660 and 1,258,412 respectively.

EP-A-0303863 describes 2-imidazolin-5-ones which are substituted in the position 4 by a group SO₂-substituted phenyl and in the position 1, by R₁₍ Rj which cannot be an aryl. These compounds are useful as intermediates and a herbicides.

DE 2658941 describes 2-imidazolin-5-ones, as synthesis intermediates, in which formula Rj is an optically active residue, deriving from an optically active primary amine or from an optically active amino-acid. No pesticidal activity is described for these compounds .

No agricultural fungicidal activity has been described for compounds of formula I.

The compounds of formula Ia are novel:

BAD ORIGINAL

Λ

AP.00496

with the proviso that when R< or Rj represents hydrogen, NR4R5 is other than an optically active residue deriving from an optically active primary amine.

A) The compounds of formula lb (n = 0) can be 5 prepared according to standard processes described in the literature:

(lb)

AP/P/ 93 /00544

1°) By cyclisation of an α-amino acid amide:

-C -NH-R₄

NH(Π) with a carboxylic acid orthoester:

R₃-C(OR')₃ in which R^# represents a linear or branched alkyl radical having 1 to 4 carbon atoms.

This process has been described, for example, by J. Brunken and G, Bach in Chem. Ber., 89, pp 1363-1373 (1956) or S. Ginsburg in J. Org. Chem., 27, pp 4062-4064 (1962).

The amino acid amides of the formula II can be prepared conventionally by reacting an amine of formula RJiHj with an amino acid ester of formula III:

^r2 O

IJ

C -OR νή₂ (IID

The reaction can then be carried out according to the conditions described by J. Brunken and

G. Bach in Chem. Ber., 89, pp 1363-1373 (1956).

2°) By reaction of an amine I^NHj with an iminoester of formula IV:

AP/P/ 9 3 / 0 0 5 4 4

ROCO-C—N ^R2 (IV)

OR'

This process has been described in J. Chem. Soc., 1959, p 1648 by G. Shaw et al.

The iminoesters IV can be obtained by

AP.00496 reaction of an amino acid ester III with an imidate of formula:

NH

OR as described in Ber. dt. Chem. Ges., 47, p 2545 (1914).

3°) The compounds of formula lb in which R₃ is a hydrogen atom can be obtained by cyclisation of an isonitrile derived from amides of formula V in the presence of base.

AP/P/ 93/00544

This process has been described by Belgian 10 Patent Application No. 862,194 of 22 December 1977.

4°) The compounds of formula lb can be obtained by alkylation of compounds lb', in which R₂ is hydrogen, by a compound R₂X in basic medium according to the method described in the abovementioned Belgian

Patent Application:

5°) By reaction of an amine R₄NH₂ with an azalactone VI of formula:

AP/P/ 9 3 / 0 0 5 4 4 c

This reaction can be carried out by acid 5 catalysis (acetic acid for example) or by basic catalysis. An example of the latter case can be found in the article by Ito et al., Yakugaku Zasshi, 1975, 95(1), 28-32.

B) The compounds of formula Ia can be 10 obtained by analogy with one of the abovementioned processes by reacting hydrazine derivatives of formula R₄NR₅NH₂ in place of the amine derivatives R,NH₂.

They can also be prepared according to a

AP.00496 process which forms part of the invention, by hot cyclisation of a hydrazide of formula VII:

i¹ r⁵

Ro —C —NH—C— C NH—N-R4

II I II 0 r₂ o (VH)

The reaction is catalysed by acids. Inorganic acids, alkylsulphonic acids, arylsulphonic acids, acidic resins or carboxylic acids can be used as acid.

The reaction can be carried out in aromatic solvents, halogenated hydrocarbons, ethers, cyclic ethers, esters or alcohols.

It is carried out at a temperature between 50 10 and 150°C. The reaction is generally carried out at the reflux temperature of the solvent, the water being distilled off as it is formed.

The hydrazides of formula VII can be prepared according to one of the processes described in the literature, for example:

1) By reaction of certain hydrazines R^NRjNH^ with certain methyl, ethyl, propyl or butyl amino acid esters of formula:

Rq—C

II

-NH—C - C!,

-e — v

J ¹¹ fL O

OR

AP/P/ 9 3 / 0 0 5 4 4 as described by German Patent Application 1,089,390 of 22 September 1960 (Chem. Ab., 1962, 56, pp

4860-4862).

2) By condensation of an N-acylated amino acid with a hydrazine in the presence of papain extracts in buffered aqueous solution according to the article by Niemann and Nichols in J. Biol. chem., 143, 1942, pp 191-201.

3) By reaction of a hydrazine I^NRjNHj with an azalactone of formula VI according to the reference by J.P. Branquet et al. in Bull. Soc. Chim. de France,

1965, (10), pp 2942-2954.

The azalactones of formula VI are themselves described in the abovementioned article.

4) A preferred general access route analogous to Point 2 above comprises activating the acid in the imidazolide (Reaction a) or mixed anhydride (Reaction b) form in order to condense it with a hydrazine:

AP/P/ 9 3 / 0 0 5 4 4

a)

r₂ ⁰ r₄nr₅nh₂

b)

AP. Ο ο 4 9 6

t C1CO₂R 4- TEA

T¹ ³ II r II II o r₂ o 0 r₄nr₅nh₂

The condensation is carried out under the usual conditions for this type of reaction, as is illustrated in Examples 1 and 2.

C) Another preferred route for preparing the 5 compounds of formula Ia comprises reacting a hydrazine RJJRjNHj with an azalactone VI under certain conditions:

1°) By heating the reactants in an inert solvent in the presence of an acid in order to catalyse the reaction. Halogenated hydrocarbons, esters, aromatic solvents or alcohols can be used as solvent.

Inorganic acids, alkylsulphonic acids, arylsulphonic acids, acidic resins or carboxylic acids can be used to catalyse the reaction. The reaction is carried out at a temperature from 50 to 150°C.

This process is illustrated in Example 4.

2°) By heating the mixture of the reactants

AP/P/ 9 3 / 0 0 5 4 4 in acetic acid at reflux in the presence of sodium acetate in order to catalyse the reaction.

These conditions are illustrated in Example 5. D) The compounds of formula (Ia), in which R₅ is other than a hydrogen atom, are also possible starting from compounds Ia' which can be alkylated, alkoxycarbonylated, acylated, arylcarbonylated, alkylsulphonylated, arylsulphonylated, carbamoylated or sulphamoylated by R_SX in the presence of base and solvent:

(la’) ^H

Rj here represents an alkyl, alkoxycarbonyl, acyl, arylcarbonyl, alkylsulphonyl, arylsulphonyl, carbamoyl or sulphamoyl group, as defined above.

X represents a halogen, a sulphate or 15 optionally substituted phenoxy group, or an alkylsulphonyloxy or arylsulphonyloxy group, or a group R_SO, when R_s is acyl.

Alkali metal hydrides, alkoxides or a tertiary amine can be used as base. The reaction can be carried out at a temperature between -30°C and +50°C. Ethers, cyclic ethers, dimethylformamide, dimethyl sulphoxide or aromatic solvents, for example, can be

WS00/C6 /d/dV ··*>

Sr used as solvent.

The carbamoylation or the thiocarbamoylation of the compounds (la') can be carried out by reaction with isocyanates or isothiocyanates according to the scheme:

The reaction is carried out under the same conditions as those described above, it being possible, however, for the base to be used in a catalytic amount.

E) The compounds of formula la in which the group R₃ is a hydrogen atom can be obtained by reaction of dimethylformamide dimethyl acetal (DMFDMA) with an aminohydrazide of formula VIII according to the scheme:

h₂nR ' 4 il .NH—N .ζ.....'r₅’ (CHj)₂NCH(OCH₃)₂ ^Ri

VIII

Έ·Δ

Re la

AP/P/ 9 3 / 0 0 5 4 4

The reaction is carried out at a temperature between 10 and 100*C in DMFDMA used in excess.

The intermediate aminohydrazides of formula VIII can be obtained according to a new process by reacting the hydrochloride of the acid chloride of the corresponding o-amino acid in the presence of a base according to the scheme:

Ri ci h₃nz^C1 ^R₄

-ζ + h₂n-n_x0 Re h₂nVIII

The reaction is carried out at a temperature 5 between -20^eC and 40^eC in cyclic or noncyclic ethers.

Nitrogenous organic bases such as triethylamine or pyridine can be optionally used as base. The intermediate acid chlorides can be obtained by the method described by S. Levine in J. Am. Chem. Soc. of

1953, Volume 76, page 1392. They are then obtained by reacting phosphorus pentachloride with the α-amino acid according to the scheme below:

AP/P/ 93/00544 h₂n1 OH “X ⁺

O

PCI, ₊ 11 Cl Cl h₃n—— o

The compounds which are preferred for their better fungicidal activity and/or for their ease of synthesis are:

1) the compounds of formula la,

2) the compounds of formula I, in particular Ia, in which R_s is a hydrogen atom,

3) the compounds in which and R_a are other

AP.00496 than H,

4) the compounds in which R₂ represents an alkyl group containing 1 to 3 carbon atoms, preferably methyl,

5) the compounds in which R₃ represents the phenyl ring, optionally substituted by R₇,

6) the compounds in which R₃ represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, methoxy or methylthio,

7) the compounds in which R₄ represents the phenyl ring, optionally substituted by R₇,

8) the compounds of formula I in which W represents an oxygen atom.

The examples below are given by way of illustration of the compounds according to the invention, of the processes for their preparation and of their antifungal properties.

The structures of all the products were established by at least 1 of the following spectral techniques: proton NMR spectrometry, carbon-13 NMR spectrometry, infrared spectrometry or mass spectrometry.

In the tables below, the methyl, ethyl, propyl, butyl and phenyl radicals are represented respectively by Me, Et, Pr, Bu and Ph, and M.p. means melting point:

AP/P/ 9 3 / 0 0 5 4 4

Example 1: This example illustrates the

G 10 c

c preparation of a hydrazide (VII) according to Process B 4a): preparation of 2-propionylamino-2-phenyl2'-phenylpropionohydrazide (compound 102):

4.51 g (0.0278 mol) of N,N'-carbonyldiimidazole are added to a solution, stirred under an inert atmosphere, of 5.6 g (0.0253 mol) of N-propionyl2-methyl-2-phenylglycine in 150 ml of anhydrous dichloromethane and the mixture is allowed to react until gas evolution has ceased. 3.28 g (0.0304 mol) of phenylhydrazine are then added and the mixture is allowed to react for 12 hours. The reaction mixture is then concentrated under reduced pressure and the residue obtained is chromatographed on 400 g of SiO₂, the eluent being an ethyl acetate/heptane (65 %/35 %) mixture. The advantageous fractions are then concentrated under reduced pressure. 4.80 g (0.0154 mol) of 2-propionylamino-2-phenyl2'-phenylpropionohydrazide, melting at 144^eC, are thus recovered with a yield of 61 %.

By carrying out the reaction according to the same procedure, Compounds 101 to 109 and 112, collated in the following table, are obtained, which are intermediates of Compounds 1 to 9 and 12:

93/00544 —NH —c— C-NHCH H ^CH3 o

-NHAP.00496

No.	Ri	r₃	r₄	Yd	M.p.
101	Ph	Me	Ph	53 %	150°C
102	Ph	Et	Ph	61 %	144°C
103	Ph	cf₃	Ph	50 %	161°C
104	Ph	CCIj	Ph	49 %	187°C
105	Ph	nPr	Ph	55 %	102°C
106	Ph	iPr	Ph	45 %	130^eC
107	Ph	tBu	Ph	77 %	134^eC
108	4-Cl-Ph	Me	Ph	71 %	180*C
109	4-Cl-Ph	Me	2-Me-Ph	64 «	152°C
112	Ph	C1CH₂	Ph	55 %	146^eC

Example 2: Preparation of a hydrazide (VII) according to Process B 4b): phenylhydrazide of N-trifluoroacetyl-2-(4-methylphenyl) glycine:

1.38 g (5 mmol) of N-trifluoroacetyl2-(4-methylphenyl)glycine, 25 ml of anhydrous toluene and then 0.75 ml (5.5 mmol) of anhydrous triethylamine are introduced into a 100 ml round-bottomed flask. The reaction mixture is cooled to -15°C and then 0.475 ml (5 mmol) of ethyl chloroformate is run in dropwise. A white precipitate is then formed and stirring is continued at -10°C for 30 minutes.

0.5 g (4.5 mmol) of phenylhydrazine and 25 ml of anhydrous toluene are introduced into a vacuum flask and the mixture is cooled to -15°C.

The contents of the first round-bottomed flask are rapidly filtered through sintered glass into the Erlenmeyer flask containing the phenylhydrazine.

The reaction mixture is allowed to return to room

AP/P/ 9 3 / 0 0 5 4 4

temperature, washed with dilute sodium hydroxide solution and water, and then dried over MgSO« before filtering and evaporating. 1.4 g (78 % yield) are thus obtained of a white solid with a melting point equal to

162°C of formula:

ch₃

FoC—C —NH—C—C-NH-NH-f ) ³ !I T II \=/ o Ho

Example 3: This example illustrates the preparation of the compounds of formula la according to Process B, by cyclisation of compounds of formula VII: preparation of 2,4-dimethyl-4-phenyl-l-phenylamino10 2-imidazolin-5-one (compound No. 1).

A stirred solution of 1.5 g (0.005 mol) of 2-acetylamino-2-phenyl-2-'-phenylpropionohydrazide and of 0.17 g (0.001 mol) of paratoluenesulphonic acid in 25 ml of toluene is held at reflux for 7 hours, the water being removed as it is formed. The reaction mixture is then concentrated under reduced pressure and the residue obtained is chromatographed on 200 g of SiO₂, the eluent being an ethyl acetate/heptane (50 ¢/50 %, mixture. A thick oil is isolated which crystallises by triturating with diisopropyl ether.

After filtration, 0.5 g (0.0018 mol) of 2,4-dimethyl4-phenyl-l-phenylamino-2-imidazolin-5-one (compound

AP/P/ 93/00544

AP.00496

No. 1) is recovered with a yield of 36 % in the form of a white powder melting at 135^eC.

Compounds 1 to 9 and 12 of formula,

recorded in the following table, are prepared according to the same procedure with the appropriate reactants.

AP/P/ 93/00544

No .	Ri	r₃	R*	Yd %	M.p.
- 1	Ph	Me	Ph	36	135^CC
2	Ph	Et	Ph	86	honey
3	Ph	cf₃	Ph	66	104°C
4	Ph	CC1₃	Ph	14	68°C
5	Ph	nPr	Ph	84	honey
6	Ph	iPr	Ph	69	122°C
7	Ph	tBa	Ph	11	87°C
8	4-Cl-Ph	Me	Ph	54	140^eC
9	4-Q-Ph	Me	2-Me-Ph	65	142°C
12	Ph	CICHj	Ph	79	76°C
14	Ph	Et	Ph	53	78°C
15	Ph	Et	2-Me-Ph	68	107°C
16	Ph	Me	2-Me-Ph	53	180°C
18	Ph	MeOCHj	Ph	8	95°C
19	Ph	MeOCH₂	3-Cl-Ph	20	125°C
26	4-Me-Ph	Me	Ph	41	142°C
29	Ph	MeOCH₂	2-Me-Ph	54	122°C
33	4-Me-Ph	cf₃	Ph	35	166°C
45	Ph	MeOCH₂	2.3-diMe-Ph	55	91°C

(

Example 4: Preparation of a compound of formula la according to Process C 1°), 2,4-dimethyl4-phenyl-l-phenylamino-2-imidazolin-5-one (compound No. 1).

A solution containing 0.9 g (4 mmol) of

2,4-dimethyl-4-phenyl-2-oxazolin-5-one, 0.43 g (4 mmol) of ph^nylhydrazine and 0.1 g of paratoluenesulphonic acid in 30 ml of toluene is heated at reflux for one hour. The water formed is removed by azeotropic entrainment and the mixture is-concentrated under

AP/P/ 93/00544 >’>

AP.00496 reduced pressure. The crude product is then purified by chromatography on silica gel.

Compound 1 is thus obtained with a yield of

%.

According to the same procedure,

2,4-dimethyl-4-(4-chlorophenyl)-1-(2,3-dimethylphenylamino)-2-imidazolin-5-one (Compound 10) is obtained with a yield of 18 % (M.p.: 164°C).

Example 5: Preparation of a compound of 10 formula Ia according to Process C 2°): 2,4-dimethyl4- (4-chlorophenyl )-1- (2-chlorophenylamino) 2-imidazolin-5-one (compound No. 11).

A solution containing 1.5 g (6.7 mmol) of 2, 4-dimethyl-4-(4-chlorophenyl)-2-oxazolin-5-one,

0.93 g (6.7 mmol) of 2-chlorophenylhydrazine and 0.25 g of sodium acetate in 20 ml of acetic acid is heated at reflux for 2 hours. The mixture is concentrated under reduced pressure and the .residues dissolved in 150 ml of methylene chloride. The methylene chloride solution is washed with an aqueous bicarbonate solution and then with pure water. The solution is concentrated and the product purified by chromatography on silica gel, the eluent being an ethyl acetate/heptane (30 %/70 %) mixture.

Compound No. 11 is thus obtained with a yield of 43 %.

Compound 13 is obtained according to the same procedure with a yield of 33.5*%.

AP/P/ 9 3 / 0 0 5 4 4

The compounds of formula:

are obtained according to the same procedure, which compounds are collated in the following table:

No.	Rx	Rx	R«	Yd %	M.p.
13	4-Br-Ph	Me	Ph	34	147^eC
17	4-Cl-Ph	Ph	3-Cl-Ph	31	120’C
20	Ph	Me	3-Cl-Ph	43	163®C
21	4-Cl-Ph	Et	Ph	27	144^eC
22	4-Br-Ph	Me	2-Me-Ph	38	144^eC
23	4-Br-Ph	Me	2-Cl-Ph	41	145*C
24	4-Br-Ph	Et	Ph	20	110°C
25	4-Cl-Ph	Me	iPr	53	honey
30	4-F-Ph	Me	Ph	-	15O⁰C
31	PhCH₂	Me	Ph	-	192’C
32	PhCH₂.	Et	Ph	-	167°C
34	Ph	Me	4-iPr-Ph	20 %	162°C
35	Ph	Me	2,3-diMe-Ph	16 %	64^eC
36	Ph	Me	2,3-diCl-Ph	33 %	165*C
37	Ph	Me	2,4-diMe-Ph	43 %	100*C
38	Ph	Me	3,4-diMe-Ph	30 %	135*C
39	Ph	Me	4-Cl-Ph	56 %	69’C
40 <	Ph	Me	2-Cl-Ph	50 %	196^eC
41	Ph	Me	4-MePh	34 %	142°C
42	Ph	Me	2-MePh	45 %	129’C
43	Ph	Et	3-Cl-Ph	26 %	82’C

AP/P/ 93/00544

AP.00496

No.	Ri	r₃	^R«	Yd %	M.p.
44	Ph	Et	2,3-diCl-Ph	41 %	60^eC
46	Ph	Et	3,4-diMe-Ph	32 %	94^eC
47	Ph	Et	2,3-diMe-Ph	27 %	109®C
48	Ph	Et	2,4-diMe-Ph	50 %	45^eC
49	Ph	Et	4-Cl-Ph	48 %	73*C
50	Ph	Et	4-iPr-Ph	16 %	73*C
51	Ph	Et	2-Cl-Ph	56 «	84*C
52	Ph	Et	3-Me-Ph	14 %	85^eC
53	4-PhO-Ph	Me	Ph	54 %	134*C
56	4-PhO-Ph	Et	Ph	58 %	honey
59	3-Cl-Ph	Et	Ph	49 %	117^eC

Likewise, the spiro compounds 27 (yield 56 %, M.p.: 203®C) and 28 (yield 56 %, M.p.: 153^eC) of formulae:

AP/P/ 93/00544 are obtained.

Example No. 6: Preparation according to Process E of compounds of formula Ia, in which R, is a hydrogen atom, and of their intermediates of formula

VIII:

a) 4.58 g (0.0208 mol) of methylphenylglycine acid chloride hydrochloride are added, in a single step, to a solution of 2.25 g <0.0208 mol) of

( (

phenylhydrazine in 50 ml of diethyl ether and the suspension thus formed is left stirring for 18 hours. The suspension is filtered and the solid sucked dry and then redissolved in distilled water. The solution obtained is slowly basified to pH = 7-8 using a saturated sodium hydrogencarbonate solution. The precipitate thus formed is filtered and washed with distilled water and then recrystallised from isopropanol. After filtering the crystals and drying under reduced pressure at 50°C, 2 g (0.0078 mol) of (2R, 2S)-2-amino-2-phenyl-2'-phenylpropionohydrazide (Compound 155), melting at 154°C, are recovered, i.e. with a yield of 38 %.

The phenylpropionohydrazides of formula:

H₂NRi

NH—N

VIII .^R4 ^R5

AP/P/ 93/00544 were obtained according to the same procedure, which compounds are recorded in the following table:

*

AP.00496

No.	Ri	Rj	R.	r₅	Yd Z	M.p.
155	Ph	Me	Ph	H	38 %	154°C
157	Ph	Me	2-Me-Ph	H	32 %	115°C
158	Ph	Me	3-Cl-Ph	H	20 %	164°C
160	Ph	Me	2-Cl-Ph	H	68 %	112°C
161	Ph	Me	4-Cl-Ph	H	48 %	177°C
163	Ph	Me	2-F-Ph	H	43 %	112°C
164	Ph	Me	4-F-Ph	H	40 %	142*C
165	Ph	Me	3-Me-Ph	H	45 %	110°C
166	Ph	Me	4-Me-Ph	H	26 %	168°C
167	Ph	Me	3-F-Ph	H	33 %	161^eC

Likewise, the spiro compound 162 (R_x = C₄H₄,

Rj » (CHj)j, Rj - H, R₄ - Ph; yield 7 %, M.p. s 171^eC) is obtained.

b) (4R,4S)-4-(4-fluorophenyl)-4-methyl5 l-phenylamino-2-imidazolin-5-one (Compound 54).

A solution of 2.73 g (0.01 mol) of (2R,2S)-2-amino-2-(4-fluorophenyl)C 2'-phenylpropionohydrazide in 16 ml of

Ν,Ν-dimethylformamide dimethyl acetal is stirred for 48 hours. The reaction mixture is concentrated under reduced pressure. The residue obtained is then chromatographed on silica, the eluent being an n-heptane/ethyl acetate mixture in the proportion: 50/50, The fractions containing the pure product No. 54 are concentrated together under reduced pressure. 1.5 g (0.0053 mol) of (4R,4S)-4-(4-fluorophenyl)-4-methyll-phenylamino-2-imidazolin-5-one, melting at 140*C on a

AP/P/ 93/00544

Kofler-type bench, are thus recovered, i.e. a yield of

%.

The compounds of formula Ia, in which R₃ is a hydrogen atom, that is to say:

o 1 were obtained according to this procedure, which compounds are collated in the following table:

AP/P/ 93/00544

NO.		r₂		Yd	M.p.
54	4-F-Ph	Me	Ph	53 %	140°C
55	Ph	Me	Ph	38 %	129°C
57	Ph	Me	2-Me-Ph	72 %	175°C
58	Ph	Me	3-Cl-Ph	46 %	177°C
60	Ph	Me	2-Q-Ph	79 %	176^eC
61	Ph	Me	4-Cl-Ph	33 %	153°C
*62	c₆h₄	(CH₂)₂	Ph	64 %	202°C
63	Ph	Me	2-F-Ph	86 %	151°C
64	Ph	Me	4-F-Ph	40 %	124°C
65	Ph	Me	3-Me-Ph	50 %	109°C
66	Ph	Me	4-Me-Ph	41 %	127°C
67	Ph	Me	3-F-Ph	20 %	137^eC

* spiro compound

Example 7: In vivo test on Plasmopara viticpla (grape downy mildew):

An aqueous suspension of the active material to be tested is prepared, by fine milling, having the following composition:

C'

AP.00496

- active material: 60 mg

- Tween 80 surface-active agent (oleate of polycondensate of ethylene oxide with sorbitan) diluted to 10 % in water: 0.3 ml

- volume made up to 60 ml with water.

This aqueous suspension is then diluted with water to produce the desired concentration of active material.

Vine cuttings (Vitis vinifera), Chardonnay 10 variety, are grown in pots. When these seedlings are 2 months old (8 to 10-leaf stage, height of 10 to 15 cm), they are treated by spraying with the above aqueous suspension.

Seedlings used as controls are treated with 15 an aqueous solution which does not contain the active material.

After drying for 24 hours, each seedling is infected, by spraying, with an aqueous suspension of spores, of Plasmopara viticola obtained from a 4-5 day culture, and then suspended at a concentration of 100,000 units per cm³.

The infected seedlings are then incubated for two days at approximately 18®C in an atmosphere saturated with moisture and then for 5 days at approximately 20-22®C under 90-100 % relative humidity.

Reading is carried out 7 days after infecting, by comparison with the control seedlings.

Under these conditions, a good (at least

AP/P/ 93/00544

%) or complete protection is observed, at a dose of g/1, with the following compounds: 1, 2, 3, 13, 15 to

18, 20 to 22, 24, 26 to 30, 35, 37 to 57, 59 to 62, 64 to 67.

Example 8: In vivo test on Puccinia recondita (brown rust of wheat):

- active material: 60 mg

- volume made up to 60 ml with water.

Wheat, in pots, sown on a 50/50 peat/pozzolana earth substrate, is treated at the 10 cm high stage by spraying the above aqueous suspension.

After 24 hours, an aqueous suspension of spores (100,000 sp/cm³) is sprayed on the wheat; this suspension was obtained from infected seedlings. The wheat is then placed for 24 hours in an incubation cell at approximately 20°C and at 100 % relative humidity, and then for 7 to 14 days at 60 % relative humidity.

Monitoring of the condition of the seedlings is carried out between the 8th and 15th day after

AP/P/ 9 3 / 0 0 5 4 4

AP.00496 infection, by comparison with an untreated control.

Under these conditions, a good (at least 75 %) or complete protection is observed, at a dose of 1 g/1, with the following compounds: 1, 2, 3, 8, 12,

17, 21, 22, 24, 28, 30, 35, 53, 54, 56, 59.

Example 9: In vivo test on Phytophthora infestans (tomato late blight):

- active material: 60 mg

- volume made up to 60 ml with water.

Tomato seedlings (Marmande variety, are grown 20 in pots. When these seedlings are one month old (5 to

6-leaf stage, 12 to 15 cm high), they are treated by spraying the above aqueous suspension at various concentrations of the compound to be tested.

After 24 hours, each seedling is infected by 25 spraying with an aqueous suspension of spores (30,000 sp/cm³, of Phytophthora infestans.

After this infecting, the tomato seedlings are incubated for 7 days at approximately 20*C in an

AP/P/ 9 3 / 0 0 5 4 4 atmosphere saturated with moisture.

Seven days after infecting, the results obtained in the case of the seedlings treated with the active material to be tested are compared with those obtained in the case of the seedlings used as controls. Under these conditions, a good (at least 75 %) or complete protection is observed, at a dose of 1 g/1, with the following compounds: 1, 2, 13, 18, 21, 24, 49, 54.

These results clearly show the good fungicidal properties of the derivatives according to the invention against fungal diseases of plants due to fungi belonging to the most diverse families, such as the Phycomycetes, Basidiomycetes, Ascomycetes,

Adelomycetes or Fungi Imperfecti, in particular grape downy mildew, tomato late blight and brown rust of wheat.

For their practical use, the compounds according to the invention are rarely used on their own. Most often these compounds form part of compositions. These compositions, which can be used as fungicidal agents, contain, as active material, a compound (or compounds) according to the invention as described above as a mixture with solid or liquid vehicles which are acceptable in agriculture, and surface-active agents which are also acceptable in agriculture. In particular, the customary inert vehicles and the customary surface-active agents can be

AP/P/ 93/00544

AP.00496

C 10

(.

c used. These compositions also form part of the invention.

These compositions can also contain all kinds of other ingredients such as, for example, protective colloids, adhesives, thickening agents, thixotropic agents, penetration agents, stabilising agents, sequestering agents and the like. More generally, the compounds used in the invention can be used in combination with any of the solid or liquid additives which correspond to the usual formulating techniques.

Generally, the compositions according to the invention usually contain approximately 0.05 to 95 % by weight of a compound (or compounds) according to the invention (subsequently called active material), one or more solid or liquid vehicles and, optionally, one or more surface-active agents.

The term vehicle, in the present account, means a natural or synthetic, organic or inorganic material with which the compound is combined in order to facilitate its application to the plant, to seeds or to the soil. This vehicle is therefore generally inert and it has to be acceptable in agriculture, especially to the treated plant. The vehicle can be solid (clays, natural or synthetic silicates, silica, resins, waxes, solid,fertilisers, and the like) or liquid (water, alcohols, especially butanol, and the like).

The surface-active agent can be an emulsifying, dispersing or wetting agent of ionic or

AP/P/ 9 3 / 0 0 5 4 4

Γ 10 c

c nonionic type or a mixture of such surface-active agents. There may be cited, for example, salts of poly(acrylic acids), salts of lignosulphonic acids, salts of phenolsulphonic or naphthalenesulphonic acids, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty amines, substituted phenols (especially alkylphenols or arylphenols), salts of esters of sulphosuccinic acids, derivatives of taurine (especially alkyltaurates), phosphoric esters of polycondensates of ethylene oxide with alcohols or phenols, esters of fatty acids and of polyols, and the derivatives of the above compounds having sulphate, sulphonate or phosphate functional groups. The presence of at least one surface-active agent is generally indispensable where the compound and/or the inert vehicle are not soluble in water and where the vector agent of the application is water.

Thus, the compositions for agricultural use according to the invention can contain the active materials according to the invention within very wide limits, ranging from 0.05 % to 95 % (by weight). Their surface-active agent content is advantageously between 5 % and 40 % by weight.

These compositions according to the invention are themselves in fairly diverse, solid or liquid

I forms.

There may be mentioned, as solid composition forms, powders for dusting (containing the compound at

AP/P/ 9 3 / 0 0 5 4 4

AP.00496 a content of up to 100 %) and granules, especially those obtained by extrusion, by compacting, by impregnation of a granulated vehicle, or by granulation from a powder (the content of the compound in these granules being between 0.5 and 80 % for the latter cases), tablets or effervescent tablets.

The compounds of formula (I) can also be used in the form of powders for dusting; it is also possible to use a composition comprising 50 g of active material θ 10 and 950 g of talc; it is also possible to use a composition comprising 20 g of active material, 10 g of finely divided silica and 970 g of talc; these constituents are mixed and milled and the mixture is applied by dusting.

As composition forms which are liquid or intended to constitute liquid compositions during application, there may be mentioned solutions, in particular water-soluble concentrates, emulsifiable concentrates, emulsions, suspension concentrates, aerosols, wettable powders (or sprayable powder), pastes or gels.

The emulsifiable or soluble concentrates most often comprise 10 to 80 % of active material, while the ready-to-apply solutions or emulsions contain 0.001 to

20 % of active material.

In addition to the solvent, the emulsifiable concentrates can contain, when this is necessary, 2 to 20 % of suitable additives such as the stabilising

AP/P/ 9 3 / 0 0 5 4 4 t'i’*·!'··. · ’ * ...

agents, surface-active agents, penetration agents, corrosion inhibitors, dyes or adhesives mentioned above.

It is possible, by diluting these concentrates with water, to obtain emulsions of any desired concentration which are particularly suitable for application to crops.

By way of example, the composition of several emulsifiable concentrates will now be given:

EC Example 1

- active material 400 g/1

- alkaline dodecylbenzenesulphonate 24 g/1

- condensate of 10 molecules of ethylene oxide with nonylphenol 16 g/1

- cyclohexanone 200 g/1

- aromatic solvent qs 1 litre

According to another emulsifiable concentrate

AP/P/ 9 3 / 0 0 5 4 4 formula, there are used:EC Example 2

- active material 250 g

- epoxidised vegetable oil 25 g

- mixture of alkylarylsulphonate and of ether of polyglycol and fatty alcohols 100 g

- dimethylformamide 50 g

- xylpne 575 g

The suspension concentrates, which can also be applied by spraying, are prepared so as to produce a stable fluid product which does not settle out and they

AP.00496 generally contain from 10 to 75 % of active material, from 0.5 to 15 % of surface-active agents, from 0.1 to 10 % of thixotropic agents, from 0 to 10 % of suitable additives, such as antifoaming agents, corrosion inhibitors, stabilising agents, penetration agents and adhesives and, as vehicle, water or an organic liquid in which the active material has little or no solubility: certain solid organic materials or inorganic salts can be dissolved in the vehicle to help in preventing sedimentation or as antifreeze for the water.

By way of example, the composition of a suspension concentrate will now be given:

SC Example 1

- active material 500

- polycondensate of ethylene oxide with tristyrylphenyl phosphate 50

- polycondensate of ethylene oxide with alkylphenol 50

- sodium polycarboxylate 20

- ethylene glycol 50

- organopolysiloxane oil (antifoam) 1

- polysaccharide 1.5

- water 316.5 g

g g

AP/P/ 93/00544

The wettable powders (or sprayable powders) are generally prepared so that they contain 20 to 95 % of active material, and they generally contain, in addition to the solid vehicle, from 0 to 30 % of a

wetting agent, from 3 to 20 % of a dispersing agent and, when necessary, from 0.1 to 10 % of one or more stabilising agents and/or other additives, such as penetration agents, adhesives, or anticaking agents, dyes, and the like.

In order to obtain the sprayable powders or wettable powders, the active materials are intimately mixed in suitable mixers with the additional substances and the mixture is milled in mills or other suitable grinders. Sprayable powders are thereby obtained whose wettability and suspensibility are advantageous; they can be suspended in water at any desired concentration and these suspensions can be used very advantageously in particular for application to plant leaves.

Instead of wettable powders, it is possible to produce pastes. The conditions and methods for producing and using these pastes are similar to those for the wettable powders or sprayable powders.

( By way of example, various wettable powder (or sprayable powder) compositions will now be given:

AP/P/ 93/00544

WP Example 1

- active material 50 %

- condensate of ethylene oxide with fatty alcohol (wetting agent) 2.5 %

- condensate of ethylene oxide with phenylethylphenol (dispersing agent) 5 %

- chalk (inert vehicle) 42.5 %

AP.00496

WP Example 2

- active material 10 %

- condensate of 8 to 10 mol of ethylene oxide with C_n branched-type synthetic oxo alcohol (wetting agent)

- neutral calcium lignosulphonate (dispersing agent)

- calcium carbonate (inert filler) gs

0.75 % %

100 *

WP Example 3:

(' (

This wettable powder contains the ingredients as in the above example, in the below:

- active material

- wetting agent

- dispersing agent

- calcium carbonate (inert filler) qs same proportions %

1.50 % %

100 %

AP/P/ 93/00544

WP Example 4:

- active material

- condensate of ethylene oxide with fatty alcohol (wetting agent)

- condensate of ethylene oxide with phenylethylphenol (dispersing agent) %

% %

WP Example 5;

- active material 50 %

- mixture of anionic and nonionic surface-active agents (wetting agent) 2.5 %

- sodium lignosulphonate (dispersing agent) 5 %

- kaolin clay (inert vehicle) 42.5 *

The aqueous dispersions and emulsions, for example the compositions obtained by diluting a wettable powder or an emulsifiable concentrate according to the invention using water, are included within the general scope of the present invention. The emulsions can be of water-in-oil or oil-in-water type and they can have a thick consistency like that of a mayonnaise.

The compounds according to the invention can be formulated in the form of water-dispersible granules also included in the scope of the invention.

These dispersible granules, with an apparent 20 density generally between approximately 0.3 and 0.6, have a particle size generally between approximately 150 and 2,000 and preferably between 300 and 1,500 microns.

The active material content of these granules 25 is generally between approximately 1 % and 90 %, and preferably between 25 % and 90 %.

The remainder of the granule is essentially composed of a solid filler and optionally of

AP/P/ 93/00544

AP.00496

surface-active adjuvants which confer waterdispersibility properties on the granule. These granules can be essentially of two distinct types depending upon whether the filler used is soluble or insoluble in water. When the filler is water-soluble, it can be inorganic or, preferably, organic. Excellent results have been obtained with urea. In the case of an insoluble filler, the latter is preferably inorganic, such as, for example, kaolin or bentonite. It is then advantageously accompanied by surface-active agents (at an amount of 2 to 20 % by weight of the granule) of which more than half consists, for example, of at least one essentially anionic dispersing agent such as an alkali metal or alkaline-earth metal polynaphthalene sulphonate or an alkali metal or alkaline-earth metal lignosulphonate, the remainder consisting of nonionic or anionic wetting agents such as an alkali metal or alkaline-earth metal alkylnaphthalene sulphonate.

Moreover, although this is not indispensable, it is possible to add other adjuvants such as antifoaming agents.

The granule according to the invention can be prepared by mixing the required ingredients and then granulating according to several techniques known per se (pelletiser, fluid bed, atomiser, extrusion, and the like). Generally, the preparation is completed by crushing followed by sieving to the particle size chosen within the abovementioned limits.

AP/P/ 93/00544

Preferably, it is obtained by extrusion, the preparation being carried out as shown in the examples below.

DG Example 1: Dispersible granules 5 90 % by weight of active material and 10 % of urea in the pearl form are mixed in a mixer. The mixture is then milled in a pin mill. A powder is obtained which is moistened with approximately 8 % by weight of water. The damp powder is extruded in a perforated-cylinder extruder. A granule is obtained which is dried and then crushed and sieved so as to retain only the granules with a size between 150 and 2,000 microns respectively.

DG Example 2; Dispersible granules

The following constituents are mixed in a mixer:

- active material 75 %

- wetting agent (sodium alkylnaphthalene sulphonate) 2 %

- dispersing agent (sodium polynaphthalene sulphonate) 8 %

- water-insoluble inert filler (kaolin) 15 %

This mixture is granulated in a fluid bed, in the presence of water, and is then dried, crushed and sieved so as to produce granules of between 0.15 and 0.80 mm in size.

These granules can be used alone or in solution or dispersion in water so as to produce the

AP/P/ 9 3 / 0 0 5 4 4

AP.00496 required dose. They can also be used to prepare combinations with other active materials, especially fungicides, the latter being in the form of wettable powders or of granules or aqueous suspensions.

As regards the compositions .which are suitable for storing and transporting, they more advantageously contain from 0.05 to 95 % (by weight) of active substance.

A subject of the invention is also the use of r

the compounds according to the invention for combating fungal diseases of plants by preventative or curative treatment of the latter or of their growth site.

They are advantageously applied at doses of 0.005 to 5 kg/ha, and more specifically of 0.01 to

1 kg/ha.

Claims

Claims

1. Compounds containing an imidazolinone or imidazolinethione group, characterised in that they correspond to the general formula (I):

(D

5 in which:

- W is a sulphur or oxygen atom or an S=0 group

- n = 0 or 1

- A represents NR₅ or 0 or S or CR_SR₍ or S0_a or C«0. - R_x and R_a, which are identical or different,

10 represent:

- H, provided that one of the 2 groups is different from H, or

- an alkyl or haloalkyl radical containing 1 to 6 carbon atoms or

15 - an alkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl, monoalkylaminoalkyl, alkenyl or alkynyl radical containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl or cycloalkyl radical containing 3 to 7 carbon atoms or

20 ,- an aryl radical comprising phenyl, naphthyl, thienyl, furyl, pyridyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl, or methylenedioxypheny1, optionally substituted by 1 to 3 groups chosen from R,

AP/P/ 93/00544

AP. Ο Ο 4 9 6 or

- an arylalkyl, aryloxyalkyl, arylthioalkyl or arylsulphonylalkyl radical, the terms aryl and alkyl having the definitions given above or

5 - Rj and R_a can form, with the carbon to which they are bonded on the ring, a carbocycle or a heterocycle having from 5 to 7 atoms, it being possible for these rings to be fused to a phenyl, optionally substituted by 1 to 3 groups chosen from R₇;

10 - Rj represents:

- a hydrogen atom or an alkyl group containing 1 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl, haloalkyl, cyanoalkyl, thiocyanatoalkyl,

15 oxoalkyl, alkenyl or alkynyl group containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl, alkoxycarbonylalkyl or N-alkylcarbamoylalkyl group containing 3 to 6 carbon atoms or

20 - an Ν,Ν-dialkylcarbamoylalkyl group containing 4 to 8 carbon atoms;

- R₄ represents:

- a hydrogen atom when n is equal to 1 or

- an alkyl group containing 1 to 6 carbon atoms or

25 γ an alkoxyalkyl, alkylthioalkyl, haloalkyl, cyanoalkyl, thiocyanatoalkyl, alkenyl or alkynyl group containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl, alkoxycarbonylalkyl or

AP/P/ 9 3 / 0 0 5 4 4

N-alkylcarbamoylalkyl group containing 3 to 6 carbon atoms or

- an Ν,Ν-dialkylcarbamoylalkyl group containing 4 to 8 carbon atoms or

5 - an aryl radical, comprising phenyl, naphthyl, thienyl, furyl, pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, pyrimidyl, pyridazinyl, pyrazinyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl or methylenedioxyphenyl, optionally substituted by 1 to 3

C 10 groups chosen from R₇ or

- an arylalkyl, aryloxyalkyl, arylthioalkyl or arylsulphonylalkyl radical, the terms aryl and alkyl having the definitions given above or

- an amino group disubstituted by 2 identical or 15 different groups chosen from:

- an alkyl radical containing 1 to 6 carbon atoms ( - an alkoxyalkyl, alkenyl or alkynyl radical containing 3 to 6 carbon atoms

20 - a cycloalkyl radical containing 3 to 7 carbon atoms

- an arylalkyl, such as defined above, phenyl or naphthyl radical, optionally substituted by 1 to 3 groups chosen from R₇ or

25 - a thienylmethyl or furfuryl radical

I

- a pyrrolidino, piperidino, morpholino or piperazino group, optionally substituted by alkyl containing 1 to 3 carbon atoms;

AP/P/ 9 3 / 0 0 5 4 4

AP . Ο Ο 4 9 6

- R₅ represents:

- H, except when R< is H, or

- an alkyl, haloalkyl, alkylsulphonyl or haloalkylsulphonyl radical containing 1 to 6 carbon

5 atoms or

- an alkoxyalkyl, alkylthioalkyl, acyl, alkenyl, alkynyl, haloacyl, alkoxycarbonyl, haloalkoxycarbonyl, alkoxyalkyl sulphonyl or cyanoalkylsulphonyl radical containing 2 to 6 carbon atoms or

10 - an alkoxyalkoxycarbonyl, alkyl thioalkoxycarbonyl or cyanoalkoxycarbonyl radical containing 3 to 6 carbon atoms or

- a formyl radical or

- a cycloalkyl, alkoxyacyl, alkylthioacyl,

15 cyanoacyl, alkenylcarbonyl or alkynylcarbony 1 radical containing 3 to 6 carbon atoms or

- a cycloalkylcarbonyl radical containing 4 to 8 carbon atoms or

- a phenyl; arylalkylcarbonyl, especially phenyl20 acetyl and phenylpropionyl; arylcarbonyl, especially benzoyl, optionally substituted by 1 to 3 groups from R_T; thienylcarbonyl; furylcarbonyl; pyridylcarbony1; benzyloxycarbonyl; furfuryloxycarbonyl; tetrahydrofur fury loxycarbonyl ; thienylmethoxycarbony1; pyridyl25 methojfycarbonyl; phenoxycarbonyl or (phenylthio) carbonyl, the phenyl being itself optionally substituted by 1 to 3 groups from R,;

(alkylthio) carbonyl; (haloalkylthio) carbonyl;

AP/P/ 93/00544 (alkoxyalkylthio)carbonyl; (cyanoalkylthio)carbonyl; (benzylthio)carbonyl; (furfurylthio)carbonyl;

(tetrahydrofurfurylthio) carbonyl; (thienylmethylthio) carbonyl; (pyridylmethylthio)carbonyl; or arylsulphonyl

5 radical or

- a carbamoyl radical, optionally mono- or disubstituted by

- an alkyl or haloalkyl group containing 1 to 6 carbon atoms or

10 - a cycloalkyl, alkenyl or alkynyl group containing 3 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl or cyanoalkyl group containing 2 to 6 carbon atoms or

- a phenyl, optionally substituted by 1 to 3

15 R₇ groups;

- a sulphamoyl group, optionally mono- or disubstituted by

- an alkyl or haloalkyl group containing 1 to 6 carbon atoms or

20 - a cycloalkyl, alkenyl or alkynyl group containing 3 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl or cyanoalkyl group containing 2 to 6 carbon atoms or

- a phenyl, optionally substituted by 1 to 3

25 R_T groups;

- an alkylthioalkylsulphonyl group containing 3 to 8 carbon atoms or a cycloalkylsulphonyl group containing 3 to 7 carbon atoms;

AP/P/ 9 3 / 0 0 5 4 4 .< I

AP.00496

- Γί^ represent,:;:

- a hydrogen atom or

- a cyano group or

- an alkyl group containing 1 to 6 carbon atoms or a cycloalkyl group containing 3 to 7 carbon atoms or

- an acyl or alkoxycarbonyl group containing 2 to

6 carbon atoms or

- a benzoyl group, optionally substituted by 1 to 3 R₇ groups;

- R₇ represents:

- a halogen atom or

- an alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkyltnio or alkylsulphonyl radical containing 1 to 6 carbon atoms or

- a cycloalkyl, halocycloalkyl, alkenyloxy, alkynyloxy, alkenylthio or alkynylthio radical containing 3 to 6 carbon atoms or

- a nitro or cyano group or r

- an amino radical, optionally mono- or ζ disubstituted by an alkyl or acyl radical containing 1 to 6 carbon atoms or an alkoxycarbonyl radical containing 2 to 6 carbon atoms

- a phenyl, phenoxy or pyridyloxy radical, these radicals optionally being substituted;

their salts and the optically active isomers; with the provisos that: when n = 0, R, is other than an optically active residue, deriving from an optically active primary amine; when n = 1 and A is SO₂, one of the two groups R₂ and R₂ must be an aryl radical; and when n = l, a-r, is other than an optically active residue, deriving from an optically active primary amine or from an optically active amino acid.

kPSPi 93/00544

BAD ORIGINAL

2. Compounds according to Claim 1, characterised in that they correspond to the formula

Ia:

c

10 in which R, to R_s and W have the same meaning as in Claim 1, with the proviso that when R₄ or R_srepresents hydrogen, NR4R5 is other than an optically active residue deriving from an optically active primary amine.

15 3. Compounds according to Claim 1 or 2, characterised in that R₅ is a hydrogen atom.

4. Compounds according to one of Claims 1 to 3, characterised in that R, and R₂ are other than a

Γ ^v- hydrogen atom.

20 5. Compounds according to one of Claims 1 to 4, characterised in that R₂ is an alkyl group containing 1 to 3 carbon atoms.

6. Compounds according to Claim 5, characterised in that R₂ is a methyl group.

25 7. Compounds according to one of Claims 1 to 6, characterised in that R, is a phenyl, optionally substituted by a R₇ group.

* * S 0 0 / £ 6 /d/dV

8. Compounds according to one of Claims 1

AP.00496 to 7, characterised in that Rj is an alkyl group containing 1 to 3 carbon atoms, optionally substituted by one or more halogens, methoxy or methylthio.

9. Compounds according to one of Claims 1 5 to 7, characterised in that R₃ is a hydrogen atom.

10. Compounds according to one of Claims 1 to 9, characterised in that R< is a phenyl, optionally substituted by a R, group.

11. Compounds according to one of Claims 1 10 to 10, characterised in that W is an oxygen atom.

12. Fungicidal compositions comprising, in combination with one or more solid or liquid vehicles which are agriculturally acceptable and/or surfaceactive agents which are also agriculturally acceptable,

15 an (or more) active material which is a compound of formula I:

AP/P/ 93/00544 in which:

- W is a sulphur or oxygen atom or an S=O group

- n = 0 or 1

20 - A represents NR₅ or O or S or CR_JR₆ or SO₂ or C=O.

- R, and R₂, which are identical or different, represent:

- H, provided that one of the 2 groups is different from H, or

- an alkyl or haioalkyl radical containing l to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl, alkylsulphonyl5 alkyl, monoalkylaminoalkyl, alkenyl or alkynyl radical containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl or cycloalkyl radical containing 3 to 7 carbon atoms or

- an aryl radical comprising phenyl, naphthyl,

10 thienyl, furyl, pyridyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl, or methylenedioxyphenyl, optionally substituted by 1 to 3 groups chosen from R₇ or

- an arylalkyl, aryloxyalkyl, arylthioalkyl or

15 arylsulphonylalkyl radical, the terms aryl and alkyl having the definitions given above or

- R, and R₂ can form, with the carbon to which they are bonded on the ring, a carbocycle or a heterocycle having from 5 to 7 atoms, it being possible for these

20 rings to be fused to a phenyl, optionally substituted by 1 to 3 groups chosen from R₇;

- R₃ represents:

- a hydrogen atom or an alkyl group containing 1 to 6 carbon atoms or

25 - an alkoxyalkyl, alkylthioalkyl, alkylsulphonylalkyl, haioalkyl, cyanoalkyl, thiocyanatoalkyl, oxoalkyl, alkenyl or alkynyl group containing 2 to 6 carbon atoms or

AP/P/ 93/00544

AP.00496

- a dialkylaminoalkyl, alkoxycarbonylalkyl or N-alkylcarbarooylalkyl group containing 3 to 6 carbon atoms or

- an Ν,Ν-dialkylcarbamoylalkyl group containing 4 5 to 8 carbon atoms;

- R« represents:

- a hydrogen atom when n is equal to 1 or

- an alkyl group containing 1 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl, haloalkyl,

10 cyanoalkyl, thiocyanatoalkyl, alkenyl or alkynyl group containing 2 to 6 carbon atoms or

- a dialkylaminoalkyl, alkoxycarbonylalkyl or N-alkylcarbamoylalkyl group containing 3 to 6 carbon atoms or

15 - an Ν,Ν-dialkylcarbamoylalkyl group containing 4 to 8 carbon atoms or

- an aryl radical, comprising phenyl, naphthyl, thienyl, furyl, pyridyl, imidazolyl, pyrazolyl,

O pyrrolyl, triazolyl, pyrimidyl, pyridazinyl, pyrazinyl,

20 benzothienyl, benzofuryl, quinolyl, isoquinolyl or methylenedioxyphenyl, optionally substituted by l to 3 groups chosen from R, or

- an arylalkyl, aryloxyalkyl, arylthioalkyl or arylsulphonylalkyl radical, the terms aryl and alkyl

25 having the definitions given above or

- an amino group disubstituted by 2 identical or different groups chosen from:

- an alkyl radical containing 1 to 6 carbon

AP/P/ 9 3 / 0 0 5 4 4 atoms

- an alkoxyalkyl, alkenyl or alkynyl radical containing 3 to 6 carbon atoms

- a cycloalkyl radical containing 3 to 7

5 carbon atoms

- an arylalkyl, such as defined above, phenyl or naphthyl radical, optionally substituted by 1 to 3 groups chosen from R₇ or

- a thienylmethyl or furfuryl radical

10 - a pyrrolidino, piperidino, morpholino or piperazino group, optionally substituted by alkyl containing 1 to 3 carbon atoms;

- R₅ represents:

- H, except when R, is H, or

15 - an alkyl, haloalkyl, alkylsulphonyl or haloalkylsulphonyl radical containing 1 to 6 carbon atoms or (

- an alkoxyalkyl, alkylthioalkyl, acyl, alkenyl, ( alkynyl, haloacyl, alkoxycarbonyl, haloalkoxycarbonyl,

20 alkoxyalkylsulphonyl or cyanoalkylsulphonyl radical containing 2 to 6 carbon atoms or

- an alkoxy alkoxy carbonyl, alkylthioalkoxycarbonyl or cyanoalkoxycarbonyl radical containing 3 to 6 carbon atoms or

25 - a formyl radical or

- a cycloalkyl, alkoxyacyl, alkylthioacyl, cyanoacyl, alkenylcarbonyl or alkynylcarbonyl radical containing 3 to 6 carbon atoms or

AP/P/ 9 3 / 0 0 5 44

AP.00496

- a cycloalkylcarbonyl radical containing 4 to 8 carbon atoms or

- a phenyl; arylalkylcarbonyl, especially phenylacetyl and phenylpropionyl; arylcarbonyl, especially

5 benzoyl, optionally substituted by l to 3 groups from JUjj thienylcarbonyl; furylcarbonyl; pyridylcarbony 1; benzyloxycarbonyl; furfuryloxycarbonyl; tetrahydrofurfuryloxycarbonyl; thienylmethoxycarbonyl; pyridylmet hoxy carbonyl; phenoxycarbonyl or

10 (phenylthio)carbonyl, the phenyl being itself optionally substituted by 1 to 3 groups from R₇; (alkylthio)carbonyl; (haloalkylthio)carbonyl; (alkoxyalkylthio)carbonyl; (cyanoalkylthio)carbonyl; (benzylthio)carbonyl; (furfurylthio)carbonyl;

15 (tetrahydrofurfurylthio)carbonyl; (thienylmethylthio)carbonyl; (pyridylmethylthio)carbonyl; or arylsulphonyl radical or

- a carbamoyl radical, optionally mono- or disubstituted by

20 - an alkyl or haloalkyl group containing 1 to

6 carbon atoms or

- a cycloalkyl, alkenyl or alkynyl group containing 3 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl or

25 cyanoalkyl group containing 2 to 6 carbon atoms or

- a phenyl, optionally substituted by 1 to 3

R₇ groups;

- a sulphamoyl group, optionally mono- or

AP/P; 9 3 / 0 0 5 4 4

*3 ., disubstituted by

- an alkyl or haloalkyi group containing 1 to

6 carbon atoms or

- a cycloalkyl, alkenyl or alkynyl group 5 containing 3 to 6 carbon atoms or

- an alkoxyalkyl, alkylthioalkyl or cyanoalkyl group containing 2 to 6 carbon atoms or

- a phenyl, optionally substituted by 1 to 3

R₇ groups;

r

10 - an alkylthioalkylsulphonyl group containing 3 to

8 carbon atoms or a cycloalkylsulphonyl group containing 3 to 7 carbon atoms;

- R* represents:

- a hydrogen atom or

15 - a cyano group or

- an alkyl group containing 1 to 6 carbon atoms or a cycloalkyl group containing 3 to 7 carbon atoms or

- an acyl or alkoxycarbonyl group containing 2 to ( 6 carbon atoms or

20 - a benzoyl group, optionally substituted by 1 to

3 R₇ groups;

- R, represents:

- a halogen atom or

- an alkyl, haloalkyi, alkoxy, haloalkoxy,

25 alkylthio, haloalkylthio or alkylsulphonyl radical containing 1 to 6 carbon atoms or

- a cycloalkyl, halocycloalkyl, alkenyloxy, alkynyloxy, alkenylthio or alkynylthio radical

AP/P/ 9 3 / 0 0 5 44

AP.00496 containing 3 to 6 carbon atoms or

- a nitro or cyano group or

- an amino radical, optionally mono- or disubstituted by an alkyl or acyl radical containing 1 to 6 carbon atoms or an alkoxycarbonyl radical containing 2 to 6 carbon atoms

- a phenyl, phenoxy or pyridyloxy radical, these radicals optionally being substituted;

their salts and the optically active isomers.

13. Fungicidal compositions according to Claim 12, characterised in that they contain from 0.05 % to 95 % by weight of compounds according to one of Claims 1 to 11.

14. Method for the treatment of crops affected or capable of being affected by fungal diseases, characterised in that there is preventively or curatively applied an effective quantity of a compound as defined in any one of claims 1 to 11 or of a compound or composition as defined in claim 12 or 13.

15. Method according to Claim 14, characterised in that the effective dose is between 0.005 and 5 kg/ha.

16. Method according to Claim 15, characterised in that the effective dose is between 0.01 and 1 kg/ha.

17. A process for the preparation of a compound of formula (I) as defined in claim l comprising:

AP/P/ 93/00544

BAD ORIGINAL ft (a) cyclising a compound of the formula:

R,

NH(ID

c.

wherein the various symbols are as defined in claim 1 with a carboxylic acid orthoester:

R₃-C(OR')₃ in which R' represents a linear or branched alkyl radical having 1 to 4 carbon atoms;

(b) reacting a derivative of formula R₄NH₂ or R^NRjNHj with an iminoester of formula IV:

ROCO | OR' ^R2 (IV)

AP/P/ 93/00544

20 wherein R' is as defined above and the other symbols are as defined in claim 1;

(c) cyclising an isonitrile of the formula:

wherein the various symbols are as defined in claim 1;

AP.00496 (d) alkylating a compound of formula (I) in which R₂ represents H to give a compound of formula (I) in which R₂ represents alkyl;

(e) reacting a derivative of formula R₄NH₂ or R4NR₅NH₂ with an azalactone VI of formula:

wherein the various symbols are as defined in claim 1; (f) cyclising a compound of formula VII:

Ri

R<

-C —NH—C—C-NH—Nr₂ o (VII)

AP/P/ 9 3 / 0 0 5 4 4 wherein the various symbols are as hereinbefore defined in a hot solvent by acid catalysis;

(g) reacting with a compound of formula R_SX or Rj-N=C=Y a compound of formula (Ia'):

(la¹) ^H wherein represents an alkyl, acyl, arylcarbonyl, alkylsulphonyl.

alkoxycarbonyl, arylsulphonyl,

Ύ £TA carbamoyl or sulphamoyl group, as defined in claim 1; X represents a halogen, a sulphate or optionally substituted phenoxy group, or an alkylsulphonyloxy or arylsulphonyloxy group, or a group RjO, when R₅ is acyl;

5 Y represents oxygen or sulphur; and R,, R₂, R₃, R« and W are as defined in claim 1, in the presence of base and solvent; or (h) reacting dimethylformamide dimethyl acetal with an aminohydrazide of formula VIII:

VI z I

15 wherein the various symbols are as defined in claim 1; and optionally converting the compound of formula (I) thus obtained into a different compound of formula (I).

18. Process according to Claim 17(f), characterised in that the acid is chosen from the group

20 comprising inorganic acids, alkylsulphonic acids, arylsulphonic acids, acidic resins or carboxylic acids.

19. Process according to Claim 17(f), characterised in that the solvent is chosen from the group comprising aromatic solvents, halogenated

25 hydrocarbons, ethers, cyclic ethers, esters or alcohols.

20. Process according to Claim 17(f), characterised in that the temperature is between 50 and

AP/P/ 9 3 / 0 0 5 4 4

AP. Ο Ο 4 9 6

Γιο

150°C.

21. Process according to Claim 17(e), characterised in that the hydrazine of formula R^NRjNHj and the azalactone of formula VI are heated at reflux in acetic acid in the presence of sodium acetate to catalyse the reaction.

22. Process according to Claim 17(h), characterised in that the reaction is carried out at a temperature between 10 and 1OO°C, preferably in excess dimethylformamide dimethyl acetal.

AP/P/ 93/00544

ABSTRACT

1) 2-Imidazolin-5-one or 2-imidazoline5-thione derivatives;
2) they are of general formula (I):

(D in which,

- W is a sulphur or oxygen atom or an S=O group

- n = 0 or 1

- A represents NR₅ or 0 or S or CRjR^ or SO₂ or

C=O

- R, to R« represent a hydrogen atom or an optionally substituted hydrocarbon radical, especially by halogen atoms.