CA2024627A1 - Oxazolidinones and-thiones as plant-growth-regulators - Google Patents

Abstract

PS/5-17735/1+2/=

Novel Oxazolidinones and -thiones as Plant- Growth- Regulators Abstract 3-Phenyl-oxazolidine-2-one- and -2- thione-5-carboxylic acid-derivatues of the formula I
below in all their stereoisometric forms, are suitable for regulating plant-growth.
(I) In this formula X is oxygen or sulfur, A is -COO R1, -COS R1, -COO?M?CONR2R3 or COCl, R is hydrogen, halogen, mono-, di- or trihalomethyl, n is 1, 2 or 3, R1 is hydrogen, C1-C4 alkyl, C2-C6 alkenyl or C2-C6 alkynyl R2 and R3 independendently of each other are hydrogen C1-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, aryl or heterocyclyl or R2 and R3 together with the nitrogen atom, to which they are bonded, are a saturated 3- to 7 membered heterocycle, which is optionally substituted up to three times by C1-C4 alkyl, and M? is the equivalent of an alkali-metal cation or an alkaline earth metal cation or HN?(R2)3.

The invention comprises the preparation and use these compounds.

Description

~2~7 PS/5 - 1 7735/1 ~2/=

Novel Oxazolidinones and -thiones as Plant - Growth - Re~ulators The present invention relates to novel 3-phenyl-oxazolidine-2-one-or-2-~hione-5-carbox5 -lic acid derivatives in all their stereoisometric forms, to processes for their preparation, to compositions containing these active substances, and to ~he use of these active substances and compositions containing them for regulating plant growth.

US Patent Specification No. 4,013,445 discloses 1-(bis-trii:luoromethylphenyl)-2-oxo-pyrrolidine-4-carboxylic acid derivatives as herbicides and for regulating plant growth.

The use of l-phenyl-2-oxopyrrolidine-4-carboxylic acids and of derivatives thereof which are unsubstituted on the phenyl ring or which are substituted by halogen atoms and~or a trifluoromethyl group, is known from French Patent Speci~lcation 1,363,615 and US
Patent Specification 3,136,620 as active substances for influencing plant growth.

It has now been found that the 3-phenyl-oxazolidine-2-one- and-2-thione-5-carboxylic acid derivatives of this invention in all their stereoisometric forms, have goodplant-growth-regulating properties.

The 3-phenyl-oxazolidine-2-one- and-2-thione-5-carboxylic a id derivatives which are proposed according to the ~nvention are those of the formula I

10~
X~NJ4 wherein l (I) Rn X is oxygen or sulfur, A is -COORl, -COSRl, -Coo~3M~33, -CONR2R3 or -COCl;
R is hydrogen, halogen, mono-, di-or trihalomethyl, n is 1, 2 or 3 Rl is hydrogen, Cl-C4alkyl, C2-C6alkenyl or C2-C6~LIcynyl; R2 and R3 independendy of 2 ~ 2 V~

one another are hydrogen, Cl-C4alkyl, C2-C6alkenyl, C2-C6alkynyl or C3-C7cycloalkyl; or R2 and R3 together with the nitrogen atom to which they are bonded are a saturated 3- to 7-membered heterocycle, which can contain an additional hetero atom, selected from the group comprising 0, N and S and which is urlsubstituted or up to trisubstituted by Cl-C4alkyl, and M~ is the equivalent of an alkali metal cation or an alkaline earth metal cation or HN~3(R2)3.

In the above definitions halogen stands for fluorine, chlorine, bromine and iodine. AL~yl is understood as meaning straight-chain or branched aL~yl, for example methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl or tert-butyl.

AL~cenyl is understood as meaning straight-chain or branched alkenyl; for example: vinyl, allyl, 2-propenyl, methallyl, 3-butenyl, 2-butenyl, 3-pentenyl, 2-methyl-4-pentenyl and 3-hexenyl.

AL~ynyl in the definitions is understood as meaning straight-chain or branched aL~cynyl; for example: propargyl, ethinyl, 2-propinyl, 3-butinyl, 2-methyl-3-pentinyl ~nd 1,2-dimethyl-3-butinyl.

Cycloalkyl is, for example, cyclopropyl, dimethylcyclopropyl, cyclobutyl, cyclopentyl, methylcyclopentyl, cyclohexyl or cycloheptyl, but preferably cyclopropyl, cyclopentyl or cyclohexyl.

Particularly suitable cations M~3 are those of aL~cali metals, for example lithium, sodium or potassium, and those of alkaline earth metals, for example magnesium or calcium. In par-ticular, M~ is HN~3(R2)3, where the substituents R2 can be identical or different, or M~) is a cation of sodium or potassium.

When A is the arnide radical -CONR2R3, the radicals mentioned below are particularly preferred: -CONH2, -CON(CH3)2, -CON(C2Hs)2, -CON , -CON CH3 , -CON~<l, -CONH~
C2H5\CH3 (R4)m ,. , . :
.. . .
- , . .
, .

.. . .

2 ~ 2 ~ ~ 2 7 ~-- y(R4)m fi--~~(R~)m fi~--~v(R4)m -CONH ~ ~ -CONH ~ ~ -CONH ~/ ~

N (R4)m N ~ (R4)m ~ (R~)m -CONH ~ CONH ~/ N -CONH ~ ~

whereby R4 is halogen, Cl-C3aL~yl, Cl-C3aLI~oxy Cl-C3haloaLkoxy and m is 0, 1, 2 or 3 Exarnples of the heterocycles forrned by the substituents R2 and R3 together with the nitrogen atom carrying them, are pyrrolidine, pyrrole, imidazole, pyrazole, piperazine, piperidine, morpholine, pyridine, pyrimidine, thiazole, thiomorpholine, triazine and triazole.

Examples for aryl are phenyl and naphthyl, which radicals are unsubstituted or mono- to tetrasubstituted by halogen, aLkyl, aLt~oxy, alkylthio, haloaLIcyl, haloaLtcoxy, nitro, cyano, carboxyl, carbamoyl aLkoxycabonyl, aL~cylcarbonyl, aL~cylsulfonyl, sulfamoyl and aL1cylsul-famoyl.

Preferred compounds of the formula I are those in which A is -COORl or -CoC)9M~33.
Individual compounds from this group which are to be mentioned are:
3-(3,5-bis-trifluoromethyl)-oxazo]idine-2-one-5-carboxylic acid, 3-(3,5-bis-trifluoromethyl)-oxazolicline-2-one-5-carboxylic acid-methyl ester and 3-(3,5-bis-trifluoromethyl)-oxazolidine-2-one-5-carboxylic acid-tributylammonium salt.

Particularly well acting groups of compounds of the formula I are formed by the optically active compounds of the formulae (R)-I and (S)-I

.

.
'' ' ~' . ' .
.
: .

5 ~ 7 A A
r~ r ~
X~\NJ X~NJ

FaC~ (R)~ (S)-(l) where A is as defined in formula I. Compounds from this group which are particularly noticeable by their good biological action are those in which A is -COORl or -COO~M~.
The following are to be mentioned as preferred individual compounds of the formulae (R)-I and (S)-I:

5-(R)-3-(3,5-bis-trifluoromethylphenyl)-oxazolidine-2-one-5-carboxylic acid 5-(R)-3-(3,5-bis-trifluoromethylphenyl)-oxazolidine-2-thioine-5-carboxylic acid-methyl ester.
5-(S)-3-(3,5-bis-trifluoromethylphenyl)-oxazolidine-2-one-5 -carboxylic acid and5-(S)-3-(3,5-bis-~rifluorornethylphenyl)-oxazolidine-2-thione-5 -carboxylic acid-methyl ester.

The compound of the formula I according to the invention can be prepared in a manner known per se by reacting, in the case of the racemic compounds of Ihe fonnula I, an aniline of the formula II

~ (II) Rn wherein n and R have the meaning given under formula I, is reacted with racemic glycidol ((+)-2,3-epoxy-1-propanol) of the formula III
O ,.
CH2!CH- CH2- OH (II~) `
to the 1,2-propanediolanillde of the formula IV

` :

' , .

- s -OH

~ (IV) Rn wherein n and R have the meaning given under formula I, and then cyclysing this diol in an appropriate solvent, in the presence of a base, with diethylcarbonate to forrn a 3-phenyl-5-hydroxymethyloxazolidine of the formula V, o CH20H
0~

Rn wherein n and R have the meaning given under foImula I, and oxydizing this compound by means of an oxydizing agent to form a 3-phenyl-oxazolidone-2-one-5-carboxylic acid of the formula Ia COOH
O
O~N~
(Ia~

R n wherein n and R have the meaning given under forrnula I, and if desired transforming this acid in a manner known per se to:a salt or by reacting it with a compound formula VI
H-B: (VI) .
. , .

' .

~,C~2~l wherein B is the radical of an alcohol, a mercaptane or of an amine, to form an ester, thioester or amide of the formula Ib o~NJ
(Ib) Rn wherein A n and R have the meaning given under forrnula I.

An ester of Ihe formula Ic o~J
~1~ (Ic) ,` ~J
Rn wherein A', n and R have the meaning given under formula Ic can optionally be ~ansformed to a 3-phenyloxazolidine-2-thione-~-carboxylic acid derivative of thefolmula Id, o S~
` 66i~ (Id) Rn - wherein n and R have the meaning given under formula I and A' is COORl and R

~. .

2~2~2~

Cl-C4alkyl, by means 2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-dipllosphethane-2,4-disul-fide (Lawesson's reagent) or with another reagent capable of intro~ucing the thioxy group.

Reagents which are suitable for introducing the thioxo group are, for example, phosphorus pentasulfide and the arylthionophosphine sulfides derived therefrom. Such reagents are described e.g. in Tetrahedron 4l 5061-5087 (1985).

Reactions for producing the compounds of the formula V are known and disclosed e.g. in Tetrahedron 45, 1323-1326 (1989~, Chimie Thérapeutique 1973, 324-327 or the French patent No 2, 458, 547.

The oxydation of the 3-phenyl-5-hydroxymethyl-oxazolidine-2-one of the formula V to the 3-phenyl-5-oxazolidine-2-one-5-carboxylic acid of the formula Ia is carried out accor-ding to Jones (Fieser and Fieser, "Reagents for Organic Synthesis", John Wiley and Sons, N.Y. Vol I 1967 p. 142) in an aprotic organic solvent, at a low temperature of bet-ween-10C to room temperature, by means of a chromic-anhydride/sulfuric acid mixture.
Appropriate solvents for this oxydation are ketones, such as acetone, methylethylketone, acetophenone, cyclohexanone, dioxane or higher molecular ethers such as tetrahydrofuane or diisopropylether.

The optically active isomers of the formula I, which are represented by the sub-formulae (R)-I and (S)-I are likewise a subject of the present invention. They can be prepared in a manner known per se, by starting in the reactions sequence given above, with optically active glycidol of the formula ((+)-III) or ((-)-III), which is commercially available, or from a racemic 3-phenyl-oxazolidine-2-one-5-carboxylic acid of the formula Ia COOH
O
O~N~
,~1~ (Ia) Rn wherein n and R have the meaning given under formula I, which is converted by fractional , , . ~

-erystallization, in a method known per se, in the presence of a chiral auxiliary, for example an optically active base, in particlllar an optically active 1-phenylethylamine, into the optically active 5-(R)(-)-3-phenyl-oxazolidine-2-one-5-earboxylie aeid of the formula (R)-Ia ~COOH

O~NJ
(R)-(Ia) Rn wherein n and R have the meaning given under formula I, and the optieally aetive 5-(S)(+)-3-phenyl-oxazolidine-2-one-5-carboxyl;e aeid of the forrmula (S)-Ia " COO~I
~"
O~NJ
(S)-(Ia), Rn wherein n and R have the meaning given under formula I and, if desired, these isomers are eonveIted in a manner known per se, into the derivatives aeeording to the definition of the forrnula (R)-Ie and (S)-Ie, O ~ A
o ~NJ o~
(R~-(lc) ~ (S)-ac) Rn Rn 2 ~ 2V~

where A' is -COORl and Rl is Cl-C4alkyl and n and R have the meaning given under for-mula I.

By subsequent reaction with a reagent capable of introducing the thioxo g~oup, the colTesponding compounds of the formulae (R)-Id and (S)-Id are obtained A' A~
0~ 0 "
S~NJ S~
[~ (R)~ (S)-(ld Rn Rn wherein A' is -COORl and Rl is Cl-C4alkyl, and n and R are as deflned under formula I, and these compounds can if desired then be converted, in a manner known per se, into the other derivatives according fo the definition, of the formulae (R)-Ie and (S)-Ie A A
O ~ O ""
S~NJ S~
(R)-(le)~ (S)~

Rn Rn where in A n and E~ are as defined in formula I.

Reagents which are suitable for introducing the thioxo group are, for example, phosphorus pentasulfide and the arylthionophosphine sulfides derived therefrom. Such reagents are described e.g. in Tetrahedron 41 5061-5087 (1985). 2,4-Bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide (Lawesson's reagent) has proved to be a particularly highly sui~able reagent for introducing the thioxo group.

ri~

- 10 ~

The compounds of the forrnula (R)-Ia and (S)-Ia are converted into the other derivatives of the fo~nulae (R)-Ib and (S)-Ib, respectively, according to the definition, in a manner known per se, for example:

by reacting the free carboxylic acids or the corresponding acid chlorides with alcohols RlOH, or by esterifying the free carboxylic acid by generally known methods.

The racemic 3,phenyloxazolidine-2-thione-5-carboxylic esters of the formule Ie and their optically active isomers of the fonnulae (R)-Ie and (S)-Ie are converted into the other derivatives of the formula Ie according to the definition in a manner known per se, for example:

- to give the free carboxylic acids (A = -COOH), by acid hydrolysis of the esters of the formulae II, (R)-IIb or (S)-IIb.

- to give the acid chlorides (A = -COCI), by reacting the free carboxylic acids with suitable chlorinating agents, for exarnple thionyl chloride, oxalyl chloride, phosgene or PCIs.

~ R2 - to give amides (A = -CO-N \ ), by reacting the acid esters, acid chlorides or free carboxylic acids with amines ~R2 N\

- to give thioesters (A = -COSR1), by reacting ~he acid chloride with mercaptans HSR1;

^ to give alkali metal salts or alkaline earth metal salts, by reacting the free carbo7~ylic acids with hydroxides, alcoholates or carbonates of alkali metals or alkaline earth metals, such as Na, K, Li, Ca and Mg hydroxide, sodium methylate, potassium methylate, sodium ethylate and potassium ethylate;
.

~2~2 ~

- to give amine salts, by reacting the free carboxylic acid with amines N(R2)3.

The invention also relates to plant-growth regulating compositions containing a novel active substance of the formula 1, and to methods for inhibiting plant growth.

Plant growth regulators are substances which cause agronomically desired biochemi~al and/or physiological and/or morphological alterations in/on the plant.

The active substances contained in the compositions according to the invention have various effects on the plant growth, depending on the point in time of application, the dosage, dle type of application and the environmental conditions. For example, plant growth regulators of the formula I can inhibit the vegetative grDwth of plants. This type of action is interesting on lawns, in the production of ornamental plants, in orchards, on verges, on sports grounds and industrial terrain, but also in the targeted inhibition of secondary shoots, such as in tobacco. In arable farming, inhibition of the vegetative growth in cereals by means of thickened stems results in reduced lodging, and similar agronomical effects are achieved in oil seed rape, sunflowers, maize and other crop plants.
Moreover, inhibition of the vegetative growth makes it possible to increase the number of plants per unit area. Another field of application of growth inhibitors is the selective control of ground-cover plants in plantations or crops with substantial distances between the rows by powerful inhibition of growth without killing these ground-cover plants, which results in the elimination of competition with the main crop but agronomically posi-tive effects, such as prevention of erosion, nitrogen ~1xation and loosening of the soil, are retained.

~ method for inhibiting plant growth is taken to mean that man interferes with the rratural development of the plant without altering, in the sense of a mutation, the life cycle of the plant which is determined by the genetic make-up. The method of growth regulation is applied at a point in time of development of the plant to be determined in the individual case. The active substances of the formula I can be applied before or after emergence of the plants, for example as early as in the seed stage, or to the seedlings, to roots, tubers, stalks, leaves, flowers or other parts of the plant. This can be effected for example by applying the active substance itself or in the form of an agent to the plants and/or by treating the culture substrate of the plant (soil).

:, .
:

It is preferred to employ the compounds of the formula I according to the in-/ention for inhibiting the growth in dicotyledon crops by post-emergence application.

The compounds of the formula I are employed as they are, or preferably as agents in conjuntion with the auxiliaries conventionally used in formulations, and as such are pro-cessed by known methods ~o give, for example, emulsion concentrates, directly sprayable cr dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granu-les and capsules, for example in polymeric subtstances. The method of application, such as spraying, atomization, dusting, scattering or watering, is chosen, as is the type of agent, according to the intended purpose and the prevailing conditions.

The formulations, i.e., the agents, preparations or compositions containing the active substance of the formuia I and, if desired, a solid or liquid additive, are prepared in a known manner, for example by intimately mixing and/or grinding the active substances with extenders, for example with solvents, solid carriers, and, if desired, surface-active compounds (surfactants~.

The following are suitable as solvents: aromatic hydrocarbons, preferably the fractions Cg to Cl2, -for example xylene mixtures or substituted naphthalenes, phthalic esters, such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons, such as cyclohexane or pa-raffins, alcohols and glycols as well as the* ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl ether or ethylene glycol monoethyl ether, ketones, such as cyclohexanone, strongly polar solvents, such as N-methyl-2-pyIrolidone, dimethyl sulfoxide or dimethylforrnamide, and epoxidized or unepoxidized vegetable oils, such as epoxidized coconut oil or soya oil; or water.

Examples of solid carriers which are generally used, for example for dusts and dispersible powders, are natural ground minerals, such as calcite, talc, kaolin, montmorillonite or atta-pulgite. To improve the physical properties, it is also possible to add highly-disperse silica or highly-disperse, absorptive polymers. Particulate, absorptive granule carriers are porous types, for example pumice, brick grit, sepiolite or bentonite, and examples of non-sorptive carrier materials are calcite or sand. Moreover, a large number of pregranulated materials of inorganic or organic nature, such as, in particular, dolomite or cornminuted plant resi-dues, can be used.

Suitable surface-active compounds aro non-ionic, cationic and/or anionic surfactants .
. . .
. .
:
' -r~

having good emulsifying, dispersing and wetting properties, depending on the nature of the active substance of the forrnula I to be formulated. Surfactants are also understood as meaning mixtures of surfactants.

Anionic surfactants which are suitable can be either so-called wateI-soluble soaps or water-soluble synthetic surface-active compounds.

Soaps which may be mentioned are the aL"ali metal salts, aL"aline eaIth metal salts or sub-stituted or unsubstituted ammonium salts of higher fatty acids (Cl0-~22), for example the Na or K salts of oleic or stearic acid, or of natural mixtures of fatty acids which can be obtained from, for example, coconut or tallow oil. Mention must also be made of the fatty acid methyl-taurinates.

However, so-called synthetic surfactants are used more frequently, in particular fa~ty sulfonates, fatty sulfates, sulfonated benzimidazole derivatives or aLtcylarylsulfonates.

The fatty sulfates or fatty sulfonates are usually in the form of alkali metal salts, alkaline earth metal salts or substituted or unsubstituted ammonium salts and have an alkyl radical having 8 to 22 C atoms, alkyl also including the aLkyl rnoiety of acyl radicals, for example the Na or Ca salt of ligninsulfonic acid, of the dodecylsulfuric ester or of a fatty alcohol sulfate mixture prepared from natural fatty acids. This group also includes the salts of the sulfuric esters and sulfonic acids of fatty alcohol/ethylene oxide adducts. The sulfonated benzimidazole derivatives preferably contain 2 sulfonyl groups and a fatty acid radical having 8 to 22 C atoms. Examples of alkylarylsulfonates are the Na, Ca or triethanolamine salts of dodecylbenzenesulfonic acid, of dibutylnaphthalenesulfonic acid or of anaphthalenesulfonic acidlforrnaldehyde condensation product.

Other suitable compounds are appropriate phosphates, for example salts of the phosphoAc ester of a p-nonylphenol/(4-14)-ethylene oxide adduct, or phospholipids.

Suitable non-ionic surfactants are mainly polyglycol ether derivatives of aliphatic or cycloaliphatic alcohols, saturated or unsaturated fatty acids and alkylphenols which can contain 3 to 10 glycol ether groups and 8 to 20 carbon atoms in the (aliphatic) hydro-carbon radical and 6 to 18 carbon atoms in the alkyl radical of the alkylphenols.

Other suitable non-ionic surfactants are the water-soluble polyethylene oxide adducts with .
.

~ ~ 2 ~

1~ -polypropylene glycol, ethylenediaminopolypropylene glycol ~nd all~ylpolypropylene gly-col which have 1 to 10 carbon atoms in the alkyl chain and contain 20 to 250 ethylene glycol ether groups and 10 to 100 propylene glycol ether groups, the abovementioned compounds generally containing 1 to 5 ethylene glycol units per propylene glycol unit.

Examples of non-ionic surfactants which may be mentioned are nonylphenolpolyethoxy-ethanols, castor oil polyethylene glycol ether, polypropylene/polyethylene oxide adducts, tributylphenoxypolyethoxyethanol, polyethylene glycol and octylphenoxypolyethoxyetha-nol.

Other suitable substances are fatty acid esters of polyoxyethylene sorbitan, such as polyoxyethylene sorbitan trioleate.

The cationic surfactants are mainly quaternary ammonium salts which contain at least one alkyl radical having 8 to 22 C atoms as N-substituents and lower, halogenated or unhalo-genated alkyl, benzyl or lower hydroxyalkyl radicals as further substituents. The salts are preferably in the form of halides, methylsulfates or ethylsulfates, for example stearyltrime-thylammonium chloride or benzyldi(2-chloroethyl)-ethylamrnonium bromide.

The surfactants conventionally used in the art of forrnulation are described, inter alia, in the following publications:

"Mc Cutcheon's Detergents and Emulsifiers Annual" MC Publishing Corp., Ridgewood, New Jersey, 1981;
H. Stache, "Tensid-Taschenbuch" [Surfactants Guide], 2nd edition, C. Hanser Verlag, Munich, Vienna, 1981;
M. and J. Ash. "EnGyclopedia of Surfactants", Vol. I-III, Chemical Publishing Co., New York, 1980-1981.

As a rule, the agrochernical preparations contain 0.1 to 95 %, in particular 0.1 to 80 %, of active substance of the formula I, 1 to 99.9 % of a solid or liquid additive and 0 to 25 %, in particular 0.1 to 25 %, of a surfactant.

PrefeIred formulations have particularly the following compositions: (% = per cent by weight).

~2~

Emulsifiable concentrate:
Active ingredient. 1 to 20 %, preferred: 5 to 10 %
Surface-active agent: 5 to 30 %, preferably 10 to 20 %
Liquid carrier: 50 to 94 %, preferably 70 to 85 %

Dusts:
Active ingredient: 0.1 to 10 %, preferably 0.1 to 1 %
Solid carrier: 99.9 to 90 %, preferably 99.9 to 99 %

Suspension concentrates:
Active ingredient: 5 to 75 %, preferably 10 to 50 %
Water: 94 to 24 %, preferably g8 to 30 %
Surface-active agent: 1 to 40 %, preferably 2 to 30 %

Wettable powder:
Active ingredient: 0.5 to 90 %, preferably 1 to 80 %
Surface-active agent: O.S to 20 %, preferably 1 to 15 %
Solid carrier: 5 to 99 %, preferably 15 to 90 %

Granules:
Active ingredient: 0.5 to 30 %, preferably 3 to 15 %
Solid carrier: 99.5 tO 70 %, preferably 97 to 85%

While relatively concentrated agents are preferred as merchandise, ehe end user, as a rule, uses dilute agents. The use forms can be diluted down to 0.001 % of active substance. As a rule, the application rates are 0.01 to 10 kg of active compound/ha, preferably 0.025 to 5 kg of active compoundlha.

The agents can also contain other additives, such as stabilizers, defoamers, viscosity regu-lators, binders, tackifiers as well as fertilizers or other active substances for achieving specific effects.

Preparation Examples The following examples illustrate the preparation of some compounds according to this mventlon.

- !

2 ~ ~ 2 ~

Example 1: Preparation of racemic 3-(3,5-bis-trifluoromethyl-phenyl)-5-carboxyl-oxazoli-done-2-one.

~;~ o~NJ
~ OXYDATION

F3C~CF3 F3C~CF3 To a solution of 24.7 g (0.075 mole) of 3-(3,5-bis-trifluoromethyl-phenyl)-5-hydroxy-methyl-oxazolidine-2-one in 500 ml of acetone which is cooled down to 0CC, is added dropwise, while stirring, 62 ml of chromic anhydride/sul~onic acid mixture (3.25 rnole C~03 in 5.29 mol H2SO4). (The starting material was prepared according to the method described in Chimie thérapeutique 1973 324-327 from 3,5-bis-trifluoromethylaniline and racemic glycidal). After the addition is completed, the reaction mixture is stirred for 14 hours at room temperature. To the green suspension thus obtained is then added, first 100 ml of isopropanol, then 1 1 of ethyl-ether and finally 1 1 of saturated salt solution.
After all the chrome salts have dissolved, the organic layer is separated and the aqueous layer extracted with ether. The organic phase is dried over magnesium-sulfate and concen-trated in a rotatory evaporator. The residue crystallized to give 25.86 g of a tan-coloured substance which, after recrystallisation from ether/petrolether leaves 19.42 g of tide-pro-duct in the form of white crystals which have a melting point at 165-169C.

Example 2: Preparation of racemic 3-(3,5-bis-trifluoromethyl)-5-methoxycarbonyl-oxazo-lidine-2-one O ~ COOCH3 O I COOH
O~NJ O~NJ

~ J~

A mixture consisting of 52.2 g (0.152 mole) of 3-(3,5-bis-~ifluoromethylphenyl)-5-car-boxyl-oxazolidine-2-one (example 1) and 77.8 g of (~)Amberlyst-resin (20 to 50 mesh, strongly acid) and 60 ml of absolute methanol is heated under reflux for two hours and then left standing overnight. The resin is then filtered off and the filtrate concentrated in a rotatory evaporator. The brown oily residue is taken up in ethyl-ether, washed neutral with sodium-bicarbonate solution and then with water, died over magnesium-sulfate and evapo-rated to dryness.

In this manner, one isolates 50.9 g of crude 3-(3,5-difluoromethyl-phenyl) -5-methoxy-car-bonyl-oxazolidine-2-one as an orange-coloured oil. This is dissolved in methylene-chlori-de and mixed with silicium-oxide. After filtering off the silicic acid, the solution is evaporated to dryness and the residue is taken up in petrol ether and well triturated. The crystals which have formed are filtered off and dried under vacuo at 40C. In thus manner 45.9 g (84,5 % of the theorie) of methyl ester is obtained in the form of white crystals, which melt at 71-74C.

In an analogous manner, the compounds of Table 1 are prepared.

/A

o~NJ
(Ib) Rn : ..

2~2~

Table 1:
Compound No. A Rn phys. data _ 1.01 (R)-COOCH3 3,5 (CF3)2 mp. 86 1.02 + -COOCH3 3,5(CF3)2 mp. 71-74 1.03 (S)-COOCH3 3,5 (CF3)2 1.04 (R)-COOH 3,5 (CF3)2 1.05 (S)-COOH 3,5 (CF3)2 1.06 + -COOH 3,5 (CF3)2 mp. 165 -169 1.07 (R)-COOCH2CH3 3,5 Cl2 1.08 (S)-COOCEI2CH3 3,5 Cl2 1.09 + -COOCH2CH3 3,5 Cl2 1.10 (R)-COO-CH-CH3 3,5 F2 1.11 (S)-COO-CH-CH3 3,5 F2 1.12 + -COO-CH-CH3 3,5 F2 1.13 (R)-COO-CH2CH2CH2CH3 3,5 Br2 1.14 (S)-COO-CH2CH2CH2CH3 3,5 Br2 1.15 + -COO-CH2CH2CH2CH3 3,5 Br2 1.16 (R)-COO-tert.-C4H9 3,5 (CF3)2 1.17 (S)-COO-tert.-C4H9 3,5 (CF3)2 1.18 i -COO-tert.-C4Hg 3,5 (CF3)2 mp. 137 -139 1 .19 (R)-coocH2-cH=cH2 3-Cl 1.20 (S)-COOCH2-CH=CH2 3-Cl 1.21 + -COOCH2-CH=CH2 3-Cl 1.22 (R)-COOCH2-C-CH 3,5 (CF3)2 - .

2 ~

Table 1: Continuation Compound No. A R" phys. data 1.23 (S)-COOCH2-C-CH 3,5 (CF3)2 1.24 + -COOCH2-C-CH2 3,5 (CF3)2 oil 1.25 (R)-COOCH2-CH=CH 3,5 I2 1.26 (S)-COOCH2-CH=CH 3,5 I2 1.27 + -COOCH2-CH=CH 3,5 I2 1.28 (R)-COOCH2-C_C-CH3 3 - F
1.29 (S)-COOCH2-C_C-CH3 3 - F
1.30 +-COOCH2-C-C-CH3 3 - F
1.31 (R)-COCI 3,5 (CF3)2 1.32 (S)-COCl 3,5 (CF3)2 1.33 + -COCl 3,5 (CF3)2 1.34 (R)-COSCH3 3,5 (CF3)2 1.35 (S)-COSCH3 3,5 (CF3)2 1.36 + -COSCH3 3,5 (CF3)2 mp. 54- 56 1.37 (R)-COS-n-C4H9 2, 3, 5 F3 1.38 (S)-COS-n-C4Hg 2, 3, 5 F3 1.39 + -COS-n-C4H9 2, 3, 5 F3 1.40 (R)-CON~ 3, 5 Cl2 ~ CH3 1.41 (S)-CON~ 3, 5 Cl2 , OEI3 1.42 + -CON~ 3, 5 Cl2 1.43 (Rj-COO~Na~ 3, 5 (CF3)2 1.44 (S)-COO~Na~ 3, 5 (CF3)2 1.45 + -COO~3Na~3 3, 5 (CF3)2 mp. 105 dec.
1.46 [(R)-Coo/3]2~ca2~33 3, 5 F2 1.47 [(s)-coo9]2~ca2~E3 3, 5 F2 2 ~

Table 1: Continuation Compound No. A Rnphys. data . .. . ___ ___ . _ _ 1.48 i -COO~] 2~) Ca2(33 3, 5 F2 1.49 (R) -Coo~ NH(C4Hg)3 3, 5 Cl2 1.50 (S) -Coo~33NH(C4H9)3 3, S Cl2 1.51 i -Coo~3NH(C4Hg)3 3, 5 Cl2 1.52 (R) -COO~NH4 3, 5 (CC13)2 1.53 (S) -COO~NH4 3, 5 (CC13)2 1.54 i -COO~3NH4 3, 5 (CCl3)2 1.55 (~) -CO--N~ > 3-Br 1.56 (S) -CO--N~ 3-Br 1.57 + -CO--N/~ 3-Br ~' /

1.58 (R)-CO-NH ~ 4-CF3 1.59 (S)-CO-NH ~ 4-CF3 1.60 + ~ -CO-NH ~ 4-CF3 1.61 + -COS-n-C4Hg 3, 5 (CF3)2 oil 1.62 i -COOCH2CH=CH2 3, 5 (CF3)2 oil 1.63 i -COO~H~N(n-C4Hg~3 3, 5 (Cl~3)2 mp. 65 - 72 1.64 i -co-NH ~ 3-Br mp. 132-134 :

::
' ,~ 2~A~2rl Table 1: Continuat;on Compound No. A Rl, phys. data ___ _ _ 1.65 + -CON O 3, 5 (CF3)2 mp. 150 - 151 N~
1.66 ~ -CONH ~ 3, 5 (CF3)2 mp. 50- 52 1.67 + -COOH 3, 5 Cl2 mp. 158-160 1.68 ~ -COOCH2C~CH 3,5 Cl2 m.p. 143-152 1.69 + -COOCH2CH=cH2 3,5 C12 m.p. 115-117 Formulation Examples:
Example Fl: Formulation examples of active substances of the formula I (% = per cent by wei~ht) a)Wettablepowders a) b) c) Active substance from Table 1 20 % 50 % 0.5 %
Na ligninsulfonate 5 % 5 % 5 %
Nalaurylsulfate 3 % 5 % 5 %
Na diisobutylnaphthalenesulfonate - 6 % 6 %
Octylphenol polyethylene glycol ether (7-8 mol of EO) - 2 % 2 %
Highly disperse silica 5 % 27 % 27 %
Kaolin 67 % 10 %
Sodium chloride - - 59.5 %

The active substance is thoroughly mixed with the addi~ives, and the mixture is ground thoroughly in a suitable mill. This gives wet~able powders which can be diluted with water -. .
,~

.
, 2 ~ 7 to give suspensions of any desired concentration.

b)Emulsion concentrate a) b) Active substance from Table 1 10 % 1 %
Octylphenol polyethylene glycol ether (4-5 mol o-f EO) 3 % 3 %
Ca dodecylbenzenesulfonate 3 % 3 %
Castor oil polyglycol ether (36 mol of EO) 4 % 4 %
Cyclohexanone 30 % 10 %
Xylenemixture 50 % 79 %

Emulsions of any desired concerltration can be prepared from this concentrate by dilution with water.

c) Dusts a) b) Active substance from Table 1 0.1 % 1 %
Talc 99 9 %
Kaolin ~ 99 %

Ready-to-use dusts are obtained by mixing the active substance with the carrier and grin-ding the mixture on a suitable mill.

d) Extruder granules a) b) Active substance from Table 1 10 % 1%
Na ligninsulfonate 2 % 2 %
Carboxymethylcellulose 1% 1%
Kaolin 87 % 96 %

The active substance is mixed with the additives, and the rnixture is ground and moistened with water. This mixture is extruded and then dried in a strearn of air.

e) Coated ~ranules Active substance from Table 1 3 %
Polyethylene glycol (MW 200) 3 %
Kaolin 94 %

. .

.

2 ~ ~ L~

~ 23 -The kaolin is moistened with polyethylene glycol and uniformly coated in a mixer with the finely ground active substance. In this manner, dust-free coated granules are obtained.

f) Suspensionconcentrate a) b) Active substance from Table 1 40 % 5 %
Ethylene glycol 10 % 10 %
Nonylphenol polyethylene glycol ether (1~ mol of EO) 6 % 1 %
Na ligninsulfonate 10 % 5 %
Carboxymethylcellulose 1% 1%
37 % aqueous formaldehyde solution 0.2 % 0.2 %
Silicone oil in the form of a 75 %
aqueousemulsion 0.8 % 0.8 %
Water 32 % 77 %

The finely-ground active substance is mixed intimately with the additives. In this manner, a suspension concentrate is obtained from which suspensions of any desired concentration can be prepared by dilution with water.

g) Salt solution Active substance from Table 1 5 %
Isopropylamine 1 %
Octylphenol polyethylene glycol ether (78 mol of EO) 3 %
Water 91 %

Biological examples The following exarnples illustrate the activity of some compounds according to this invention in plant-regulatory tests.

Example B 1: Inhibition of growth in tropical le~urninous cover crops The plants (for example Centrosema pubescens or Psophocarpus palustris) are propagated by cuttings in 4 cm peat pots with field soil (45 %), peat (45 %) and zonolite (10 %). They are grown in the greenhouse at a day temperature of 27C and a night temperature of 23C. The plants are illuminated for at least 14 hours/day at an intensity of at least 7000 , :- . , , ., ~ . .. . . ~ , .
. ,` ' ., . ' ' . ~ ~ , .
,. :

. . .

lux.

About 50 days after planting the cuttings, they are repotted in 13 cm pots, 4-5 plants/pot.
After a further 60 days, the plants are cut back to a height of about 15 cm, and subj~cted to the application treatment. In this treatment, they are sprayed with 0.3 to 3 kg of active sub stance/ha (formulated, as a rule, as a 25 % concentration) in an aqueous spray liquor. The amount of water applied is about 200 I/ha.

The experiment is evaluated 4 weeks after the application. In this evaluation, the additio-nal growth is scored and weighed in comparison with the control, and the phytotoxicity is rated. In ~his experiment, the plants treated with the active substances from Table 1 show a marked reduction of additional growth without inflicting damage on the experimental plants.

Example B2: Growth regulation in soya beans The plants (for example cultivar Williams) are sown in 11 cm clay pots with field soil (45 %), peat (45 %) and zonolite (10 %), and grown in a growth cabinet at a day tempe-rature of 24C and a night temperature of 19C. The plants are illuminated for a period of 16 hours per day at an intensity of about 2900 lux.

About 24 days after sowing, repotting into 18 cm pots is effected, 2 plants per pot. After a further 12 days and in the stage where 5 - 6 trifoliate leaves have appeared, up to 100 g of active substance/ha is applied to the plants, the formulation being, as a rule, 25 % concen-tration and in aqueous spray liquor. The amount of water applied is about 200 Vha.

The experiment is evaluated about 4 weeks after the application. In comparison with the untreated control plants, the active substances from Table 1 that were tested, result in a markedly reduced growth without phytotoxicity.

Example B3: Selective rowth inhibition of oil seed rape and clover in maize The compounds of Table 1 are highly suitable for selectively and strongly inhibiting cover crops in a ma;ze crop and therefore preventing the undersown crop from competing for water and nutrients, while simultaneously maintaining the agronomically desired effects of the undersown crop, such as protection from erosion, nitrogen fixation and reduction of soil compaction. This is tested for the crop combinations maize/white clover and maize/oil seed rape, as follows:

.

.

2 ~ 2 ~

"Blizzard" maize is sown in 15 cm pots with ~leld soil and grown for 15 days in the green-house at day/night temperatures of 22/19C and an illumination period of at least 13.5 hours/day in the case of post-emergence application, pre-emergence application being carried out one day after sowing.

"Bienvenue" oil seed r~pe is sown in 15 cm pots with field soil, and grown for 7 days at day/night temperatures of 22/19C, then for 17 days at 10/5C and then for 7 days at 15/10C until the application was effected.

"Ladino" white clover is grown in 15 cm pots with a mixture of field soil (60 %), peat substrate (30 %) and zonolite (10 ~o) for 40 days at day/night temperatures of 21/18C and a minimum illumination period of 13.5 hours.

All crops are fed and watered as required, the compound No. 1.01 (formulated in a 25 %
concentration) is applied in ~001 of water/ha and at application rates of 30 to 500 g/ha. 28 days after application, the height of the additional growth is measured, and the action is represented in per cent growth inhibition in comparison with the untreated control. 100 %
action denotes no additional growth at all, 0 % action denotes growth as in the untreated control.

The compoufids of Table 1 that were tested showed in this test good growth-inhibitory activity in clover and rape, while the growth of the maïze plants was not inhibited.

Example B4: Selctive growth inhibition of weeds in culture plants The compounds o~ Table 1 are also highly suitable for inhibiting selectively and strongly weeds in cultures of crop plants and therefore preventing the competitive growth of weeds, without destroying them completely. This is tested as shown below with the crop plants barley, wheat and maize and the weeds Ipomoea purpurea~ Solanum ni~um. Xanthiurnstmmarium. Chenopodium album, ~alium aparine~ Veronica persica and Chrysanthemumleucanthemum.

The above crop plants and weeds are grown in the greenhouse and when they had reached the 4- to 6-leaf stage, they were treated with an aqueous suspension of an active compound of Table 1. The treated plants are then cultivated further in the greenhouse. The test is evaluated 15 days after the treatment and the growth inhibition is given in percent (see ~`

.~ ` ' : ., ' , ' , Table 2) O= no growth inhibition, 100 % = complete stop of the growth after the treatment. As an example, the results obtained with compound 1.02 (of Table 1) are given in the Table 2 below Table 2:
Growth-inhibition at active substance/ha plants 60 125250 500 1000 barley 0 0 0 0 10 _ .
wheat 0 0 0 0 0 maize 0 0 0 0 0 Jpomoea 10 60 70 __ _. 90 Solanum 0 40 70 80 80 Xanthium 10 40 80 80 90 Chenopodium 0 20 30 70 70 Galium 10 20 70 90100 Chrysanthemum 40 60 80 90 90 . _ _ .
Veronica 30 50 60 80 90

Claims (13)

1. A 3-phenyl-oxazolidine-2-one and -2-thione-5-carboxylic acid derivative in all its stereoisometric forms of the formula I

(I) wherein X is oxygen or sulfur A is -COOR1, -COSR2, -COO?M?, CONR2R3 or COCI, R
is hydrogen, halogen, mono-, di- or trihalomethyl n is 0,1,2 or 3 R1 is hydrogen C1-C4 alkyl, C2-C6 alkenyl or C2-C6 alkynyl R2 and R3 independently of one another are hydro-gen, C1-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C3 cylcloalkyl aryl or heterocyclyl R2 and R3 together with the nitrogen atom, to which they are bonded, are a saturated 3- to 7- membered heterocycle, which can contain an additional hetero atom, selected from the group comprising O, N and S and which is unsubstituted or up to trisubstituted by C1-C4 alkyl, and M? is the equivalent of an alkaline earth metal cation or HN?(R2)3.

2. An optically active compound according to claim 1 of the formula (R)-I and (S)-l (R)-(I) (S)-(I) wherein A, n, R and X have the meaning given in claim 1.

3. A compound of the formula I according to claim 1 wherein A is -COOR1 or -COO?M?, R is halogen or trifluoromethyl, n is 1 or 2 and R1 and M? have the meaning given in claim 1.

4. A 3-phenyl-oxazolidine-2-one-5- cabonic acid-derivative according to claim 1 in all its stereoisometric forms, of the formula Ib (Ib) wherein A, n and R have the meaning given in claim 1.

5. A 3-phenyl-oxazolidine-2-thione-5-carboxylic acid derivative according to claim 1 in all its stereoisometric forms of the formula Ie (Ie) wherein A, n and R have the meaning given in claim 1.

6. A 3-phenyl-oxazolidine-2-one according to claim 1 selected from the group consisting of 3-(3,5-bis-trifluoromethylphenyl)-oxazolidine-2-one-5- carboxylic acid, 3-(3,5-bis-tri-fluoromethylphenyl)-oxazolidine-2-one-5-carboxylic acid-methyl ester, 5-(R)-3-(3,5-bis-trifluoromethylphenyl)-oxazolidine-2-one-carboxylic acid, 5-(R)-3-(3,5-bis-trifluoro-methylphenyl)-oxazolidine-5-carboxylic acid-methyl ester, S-(S)-3-(3,5-bis-trifluoro-methylphenyl)-oxazolidine-5-carboxylic acid, 5-(S)-3-bis-trifluoromethylphenyl)-oxazoli-dine-5-carboxylic acid-methyl ester and 5-(3,5-bis-trifluoromethylphenyl)-oxazolidi-ne-5-carboxylic acid-tributylammonium salt.

7. A process for preparing a 3-phenyl-oxazolidine-2-one or 3-phenyl-oxazolidine-2-thione of formula I, according to claim 1, which comprises reacting an aniline of formula II, (II) wherein n and R have the meaning given in claim 1, with a racemic glycidol ((?)2,3-epoxy-1-propanol) of formula III, (III) to the 1,2-propanediolanilide of the forrmlla IV, (IV) wherein n and R have meaning given in claim 1, and then cyclysing this diol in an appropriate solvent, in the presence of a base, with diethylcarbonate to form a 3-phenyl-5-hydroxymethyloxazolidine of the formula V, (V) wherein n and R have the meaning given in claim 1, and oxydizing this compound by means of an oxydizing agent to form a 3-phenyl-oxazolidone-2-one-5-carboxylic acid of the formula Ia (Ia) wherein n and R have the meaning given in claim 1, and if desired transforming this acid in a manner known per se to a salt or by reacting it with a compound of the formula VI
H-B (VI) wherein B is radical of an alcohol, a mercaptan or of an amine, to form an ester, thioester or amide of the formula Ib (Ib) wherein A, n and R have the meaning given in claim 1.

8. A process for the preparation of a 3-phenyl-oxazolidine-2-thione-5-caboxylic acid according to claim 1 of the formula Id, (Id) wherein n and R have the meaning given in claim 1 A' is -COOR1 and R1 is C1to C4 alkyl, which is characterised in treating a 3-phenyl-oxazolidine-2-one of the formula Ic (Ic) wherein A',n and R have the meaning given above with 2,4-bis-(4-methoxyphenyl)-1,3-dithio-2,4-diphosphethane-2,4-disulfide (Lawesson's reagent) or with another reagent capable of introducing the thioxo groups.

9. A process for the preparation of a 3-phenyl-oxazolidine-2-thione-5-carboxylic acid derivative according to claim 1 of the formula Ie, (Ie) wherein A, n and R have the meaning given in claim 1, which comprises saponifying a racemic or optically active 3-phenyl-oxazolidine-2-thione of the formula Id, (Id) wherein n and R have the meaning given in claim 1, A' is COOR1 and R1 is C1-C4 alkyl in a manner known per se, into free acid and transforming the free acid in a manner known per se into with a compound of the formula VI

H-B (VI) wherein B is the radical of an alcohol, a mercaptan or an amine, to form an ester thioester or an amide of the formula Ie.

10. A composition for regulating plant growth, containing besides inert carriers and adjuvants, as active component, a plant-growth regulatory effective amount of a 3-phenyl-oxazolidine-2-one or -2-thione of the formula I, according to claim 1.

11. A composition according to claim 10, which contains between 0.1 % and 95% of an active compound of the formul I according to claim 1.

12. A process for inhibiting plant-growth, which comprises applying to the plants or their enviroment, a plant-growth-inhibitingly effective amount of a compound of the formula I
according to claim 1 or of a composition containing such a compound.

13. A process according to claim 12, which comprises applying an amount of active substance according to claim 1 of between 0.01 and 10 kg per hectare.