FR2660307A1 - New 5,6-dihydro-2-methyl-4-[3-(trifluoromethyl)phenyl]-2H-1,2,4-oxadiazin- 3(4H)-one derivatives, process for their preparation and the intermediates of this process, their application as herbicides and the compositions which contain them - Google Patents

Abstract

The subject of the invention is the products of formula (I): in which R represents a substituted or unsubstituted, saturated or unsaturated, cyclic or acyclic radical containing from 1 to 14 carbon atoms and optionally from 1 to 4 identical or different heteroatoms, it being understood that R cannot represent an unsubstituted, saturated, acyclic hydrocarbon radical containing from 1 to 4 carbon atoms. These products have advantageous herbicidal properties.

Description

 The present invention relates to novel derivatives of 5,6-dihydro-2-methyl-4- [3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one, having at the 4-position of phenyl a -OR radical, their preparation process and the intermediates of this process, their application as herbicides and the compositions containing them.

dans laquelle R représente un radical cyclique ou acyclique, saturé ou insaturé, substitué ou non substitué, renfermant de un à quatorze atomes de carbone et éventuellement de un à quatre hétêroatomes identiques ou différents, étant entendu que R ne peut pas représenter un radical hydrocarboné acyclique, saturé et non substitué renfermant de un à quatre atomes de carbone.The subject of the invention is the products of formula (I)

in which R represents a saturated or unsaturated, substituted or unsubstituted cyclic or acyclic radical containing from one to fourteen carbon atoms and optionally from one to four identical or different hetero-atoms, it being understood that R can not represent an acyclic hydrocarbon radical; , saturated and unsubstituted having one to four carbon atoms.

 When R represents a saturated or unsaturated, substituted or unsubstituted cyclic radical, it may be a carbocyclic or heterocyclic radical.

 By saturated or unsaturated carbocyclic radical, substituted or unsubstituted, is meant mainly the cycloalkyl, cycloalkenyl, cycloalkadienyl or aryl radicals optionally substituted by one or more radicals chosen in particular from halogen atoms, alkyl, haloalkyl, polyhaloalkyl and alkyloxy radicals. , (haloalkyl) oxy, (polyhaloalkyl) oxy, alkylthio, (haloalkyl) thio, (polyhaloalkyl) thio or alkoxycarbonyl. It is preferentially cyclopropyl, cyclopentyl, cyclohexyl, 2-isopropyl-5-methylcyclohexyl, 1-cyclopentenyl, 2-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 1,3-cyclopentadienyl, 1,3-cyclohexadienyl radicals. 1,4-cyclohexadienyl, phenyl, 2-bromo phenyl, 4-bromo phenyl, 2-chlorophenyl, 4-chlorophenyl, 2-fluoro phenyl, 4-fluoro phenyl, 2-methylphenyl, 4-methylphenyl, 3 methyl phenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 3,4-dichlorophenyl, 2,4-dibromo phenyl, 2,4,5-trichlorophenyl, 3,5-dimethylphenyl, 2- methyl 4-chlorophenyl, 3-methyl-4-chlorophenyl, 4-methyl-3- (trifluoromethyl) phenyl, 3- (trifluoromethyl) phenyl, 4-methoxyphenyl, 4- (difluoromethoxy) phenyl, 4-chloro-3,5 dimethoxyphenyl, 2-chloro-5-methoxyphenyl, 4- (methylthio) phenyl, 3-methyl-4- (methylthio) phenyl or 3-ethoxycarbonylphenyl.

 By saturated or unsaturated heterocyclic radical, substituted or unsubstituted, is meant in particular heterocyclic radical isolated, fused or bridged, comprising from one to four heteroatoms selected from oxygen nitrogen or sulfur, aromatic or non-aromatic and optionally substituted and preferably the radicals, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, 1-phenyl 1H-tetrazol-5yl, pyridyl, 5-trifluoromethyl-2-pyridyl, 5-chloro-2-pyridyl, 3,5-dichloro-2-pyridyl, pyridazinyl 6-chloro-3-pyridazinyl, pyrimidinyl, 5-chloro-2-pyrimidinyl, 5-iodo-2-pyrimidinyl, 5-bromo-pyrimidinyl, 1-ethyl-3-tert-butyl, 1H-pyrazol-5-yl, 5-tert- butyl 1,3,4-thiadiazol-2-yl, indolyl, quinolyl, 6-quinolyl, 2-methyl-6-quinolyl, 3-methyl-6-quinolyl, 3-methyl-7-quinolyl, 3- (trifluoromethyl) -7-quinolyl 1-Isopropyl-4-methyl-7-oxabicyclo [2.2.1] heptan-3-yl, 1,2-benzisothiazol-5-yl, 2,2,3,3-tetrafluoro-2,3-dihydro-1,4-benzodioxin 6-yl, benzothiazol-2-yl, 3,4-dihydro-2,2-dimethyl-2H-1-penzopyran-7-yl, 2-ethyl-2,4-dihydro-2,3-dimethyl-6-benzofuranyl or 3, 4-Dihydro-2-methoxy-2,4,4-trimethyl-2H-1-benzopyran-7-yl.

 When R represents a saturated or unsaturated, substituted or unsubstituted acyclic radical, it is mainly a linear or branched, saturated or unsaturated, acyclic hydrocarbon radical containing from one to eight carbon atoms, and in particular an alkyl radical. , alkenyl, alkanedienyl or alkyne.

 When it is an alkyl radical containing from one to four carbon atoms, R is necessarily substituted; in other cases, R may be unsubstituted or substituted.

 The substituent or substituents R may carry are preferably chosen, independently of one another, from fluorine, bromine, chlorine or iodine atoms, or hydroxy, carboxy, methylsulfonyloxy, phenylsulfonyloxy, ortho, meta or para tolylsulfonyloxy groups. alkyloxy containing one to three carbon atoms linear or branched and optionally substituted by one or more atoms selected from chlorine, bromine or iodine fluorine atoms, alkylthio containing from one to three carbon atoms, linear or branched and optionally substituted by one or more atoms chosen from fluorine, chlorine, bromine or iodine atoms, alkoxycarbonyl containing from two to five carbon atoms, cycloalkyl containing from three to eight carbon atoms and optionally substituted with one or several groups chosen from fluorine, bromine or chlorine atoms or linear or branched alkyl radicals containing from one to three carbon atoms and optionally substituted by one or more chlorine, fluorine, bromine or iodine atoms, cycloalkenyl containing from five to eight carbon atoms and optionally substituted by one or more groups selected from halogen atoms or alkyl radicals, linear or branched and containing one to three carbon atoms, cycloalkadienyl containing from five to eight carbon atoms and optionally substituted by one or more groups selected from halogen atoms or linear or branched alkyl radicals and containing from one to three carbon atoms, phenyl optionally substituted by one or more groups chosen from fluorine, chlorine, bromine or iodine atoms or alkyl radicals containing from one to four linear or branched carbon atoms and optionally substituted with one or more fluorine, chlorine, bromine or iodine atoms, hydroxy, carboxy, methylsulfonyloxy, phenylsulfonyloxy, ortho, meta or para tolylsulfonyloxy, alkyloxy containing from one to three carbon atoms linear or branched and optionally substituted by one or more atoms chosen from chlorine, bromine or iodine fluorine atoms, alkylthio containing from one to three carbon atoms , linear or branched and optionally substituted with one or more atoms selected from fluorine, chlorine, bromine or iodine, alkoxycarbonyl containing from two to five carbon atoms, or isolated, fused or bridged heterocyclic groups, having one to four heteroatoms selected from sulfur, oxygen or nitrogen and optionally substituted, such as 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-ethyl-2-pyridyl, 4-methyl-2 pyridyl, 6-methyl-2-pyridyl, 4,6-dimethyl-2-pyridyl, 2-ethyl-1-oxaspiro (4.5) dec-2-yl, 2-ethyl-1,7-dioxaspiro (4.5) dec-2-yl or 2-ethyl-2-pyridyl , 3-dihydro-1,4-benzodioxin-2-yl.

dans laquelle R1 représente un radical hydrocarboné acyclique saturé ou insaturé, linéaire ou ramifié, renfermant de un à quatre atomes de carbone et substitué par un ou plusieurs radicaux choisis parmi les atomes d'halogène, les radicaux alkyloxy renfermant de un à quatre atomes de carbone, carboxy, alcoxycarbonyle renfermant de deux à cinq atomes de carbone, toxyloxy, mésyloxy, cycloalkyle renfermant de trois à six atomes de carbone ou phényle éventuellement substitué par un ou plusieurs atomes d'halogène, et spécialement ceux répondant à la formule (I2)

dans laquelle R2 représente un radical alkyle renfermant de un à trois atomes de carbone substitué par un ou plusieurs atomes de fluor et éventuellement un atome de chlore ou de brome, ceux répondant à la formule (I3) :

dans laquelle R3 représente un radical alcényle ou alcynyle renfermant de deux à quatre atomes de carbone et éventuellement substitué par un ou plusieurs atomes d'halogène et ceux répondant à la formule (I4) :

dans laquelle R4 représente un radical

dans lequel R5 représente un atome d'hydrogène ou un radical méthyle, n est égal à 1 ou 2 et m prend une des valeurs de O à 5.The subject of the invention is particularly the products defined above and corresponding to formula (I1):

in which R 1 represents a saturated or unsaturated, linear or branched, acyclic hydrocarbon radical containing from one to four carbon atoms and substituted by one or more radicals chosen from halogen atoms, alkyloxy radicals containing from one to four carbon atoms; , carboxy, alkoxycarbonyl containing from two to five carbon atoms, toxyloxy, mesyloxy, cycloalkyl containing from three to six carbon atoms or phenyl optionally substituted by one or more halogen atoms, and especially those corresponding to formula (I2)

in which R2 represents an alkyl radical containing from one to three carbon atoms substituted by one or more fluorine atoms and optionally a chlorine or bromine atom, those corresponding to formula (I3):

in which R3 represents an alkenyl or alkynyl radical containing from two to four carbon atoms and optionally substituted with one or more halogen atoms and those corresponding to formula (I4):

in which R4 represents a radical

in which R5 represents a hydrogen atom or a methyl radical, n is equal to 1 or 2 and m takes one of the values of O to 5.

Among the values defined above, R2 preferably represents a radical (difluoromethyl), (trifluoromethyl), (bromodifluoromethyl), (chlorodifluoromethyl), 2,2,2-trifluoroethyl, 2,2-difluoroethyl, 2,2-difluoro 1ethyl ethyl, 2,2,3,3-tetrafluoropropyl, 1,1,2,3,3-pentafluoropropyl, R3 preferably represents a 2propynyl radical, 2-iodo-1-fluoroethylene, 2,2-chloroethenyl, 2 , 2-dibromo ethenyl, 2-propenyl or 3-methyl-2-butenyl, and
R4 preferably represents a benzyl, phenethyl, 2-fluoro-benzyl, 3-fluoro-benzyl, 4-fluoro-benzyl, pentafluoro-benzyl, alpha-methyl-4- (trifluoromethyl) -benzyl or 4-fluoro-phenethyl radical.

 The subject of the invention is particularly the products of formula (I) as defined above and whose names follow - 4- [4- (difluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6dihydro-2-methyl-2H-1 2,4-oxadiazin-3 (4H) -one - 5,6-dihydro-4- [4 - [(4-fluoro-phenyl) -methoxy] -3- (trifluoro-romethyl) phenyl-2-methyl-2H-1,2, 4-oxadiazin-3 (4H) -one - 4- [4- (bromodifluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) - one - 4- [4 - [(1-fluoro-2-iodo-ethenyl) oxy) -3- (trifluoromethyl) -phenyl] -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) - one - 5,6-dihydro-2-methyl-4- [4- (2,2,2-trifluoroethoxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one -5 6-Dihydro-2-methyl-4- (4- (3-methyl-2-butenyloxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one -4- [4- 3,3-dichloro-2-propenyloxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one-5,6-dihydro-2-methyl 4 - [4- (2-propenyl oxy) 3- (trifluoromethyl) phenyl) 2H-1,2,4-oxadiazin-3 (4H) -one - 4- [4- (cyclopropylmethoxy) 3- (trifluoromethyl) phenyl) 5,6-dihydro-2-methyl-2H 1,2,4-oxadiazin-3 (4H) -one-5,6-dihydro-2-methyl-4- [4- (2-propynyloxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4 -oxadiazin-3 (4H) -one.

sous forme d'un sel d'acide minéral ou organique est transformée en isocyanate de formule (III)

qui, traite en présence d'une base par un sel de N-méthyl hydroxylamine de formule (IV)
CH3-NH-OH (IV) conduit au dérivé de l'urée de formule (V)

produit de formule (V) que lton fait réagir en présence d'une base et de préférence dans un solvant polaire, avec un 1,2dihalo éthane de formule (VI)
X-CH2-CH2-X (VI) dans laquelle X représente un atome de chlore ou de brome, pour obtenir le produit de formule (I).The subject of the invention is also a process for the preparation of the products of formula (I), characterized in that the amine of formula (II)

in the form of an inorganic or organic acid salt is converted into isocyanate of formula (III)

which, in the presence of a base, is treated with an N-methylhydroxylamine salt of formula (IV)
CH3-NH-OH (IV) gives the derivative of urea of formula (V)

product of formula (V) which is reacted in the presence of a base and preferably in a polar solvent with a 1,2-dihaloethane of formula (VI)
X-CH 2 -CH 2 -X (VI) wherein X represents a chlorine or bromine atom, to obtain the product of formula (I).

 In a preferred embodiment of this process the amine of formula (II) is converted into its hydrochloride by usual methods; the isocyanate conversion reagent of formula (III) may be phosgene or trichloromethyl chloroformate; the product of formula (V) is prepared by reaction of N-methylhydroxylamine hydrochloride on the isocyanate of formula (III) in a solvent such as dimethylformamide in the presence of a nitrogen base such as triethylamine or dimethylamino; pyridine and the cyclization reaction takes place in a polar solvent such as dimethylsulfoxide with 1,2-dichloroethane in the presence of a base such as potassium carbonate.

est soumis à une hydrogénation catalytique et conduit au produit de formule (VII)

que l'on transforme en présence d'une base et par action d'un réactif d'éthérification des phénols en un produit de formule (I) ou bien l'amine de formule (VIII)

sous forme d'un sel d'acide minéral ou organique est transformée en isocyanate de formule (IX)

qui, traité par un sel de N-méthyl hydroxylamine de formule (IV), conduit au dérivé de l'urée de formule (X)

produit de formule (X) que l'on fait réagir en présence d'une base et de préférence dans un solvant polaire, avec un 1,2-dihalo éthane de formule (VI) pour obtenir le produit de formule (XI)

que l'on transforme en produit de formule (I) par action d'un alcoolate alcalin préparé à partir de l'alcool de formule (XII)
R-OH (XII) avec un hydrure alcalin.The invention also relates to variants of the method described above characterized in that either the product of formula (in)

is subjected to a catalytic hydrogenation and leads to the product of formula (VII)

that is converted in the presence of a base and by action of an etherification reagent phenols in a product of formula (I) or the amine of formula (VIII)

in the form of a mineral or organic acid salt is converted into isocyanate of formula (IX)

which, treated with an N-methyl hydroxylamine salt of formula (IV), gives the urea derivative of formula (X)

product of formula (X) which is reacted in the presence of a base and preferably in a polar solvent, with a 1,2-dihaloethane of formula (VI) to obtain the product of formula (XI)

that is converted into product of formula (I) by the action of an alkali metal alcoholate prepared from the alcohol of formula (XII)
R-OH (XII) with an alkaline hydride.

 Phenol etherifying reagent generally means products which allow O-substitution of the product of formula (VII).

The amines of formula (II) or their salts are generally known or can be prepared conventionally according to the scheme

sel d'amine les produits de formules (XIII) et (VIII) sont des produits commerciaux.

amine salt the products of formulas (XIII) and (VIII) are commercial products.

 The products of formula (III), (V), (VII), (IX), (X) and (XI) are new and also objects of the present invention.

 The subject of the invention is also the use as herbicides of the products of formula (I) as defined above, particularly the use as herbicides of the products of formulas (I1), (I2), (I3) and (I4) and especially the use as herbicides of the following products - 4- (4- (difluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one - 5,6-dihydro 4- (4 - ((4-fluoro-phenyl) methoxy] -3- (trifluoromethyl) phenyl) -2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one - 4 - (4- (bromodifluoromethoxy) 3 - (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one - 4- (4- (<1 2-iodo-ethenyl) oxy) -3- (trifluoromethyl) phenyl] -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one-5,6-dihydro-2-methyl-4 - (4- (2,2,2-trifluoroethoxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one -5,6-dihydro-2-methyl-4- - (3-methyl-2-butenyloxy) 3- (trifluoromethyl) phenyl] 2H-1,2 4-oxadiazin-3 (4H) -one - 4- (4- (3,3-dichloro-2-propenyloxy) -3- (trifluoromethyl) phenyl) -5,6-dihydro-2-methyl-2H-1,2,4- oxadiazin-3 (4H) -one -5,6-dihydro-2-methyl-4- [4- (2-propenyloxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one 4- (4- (Cyclopropylmethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one-5,6-dihydro-2-methyl-4 ( 4- (2-propynyloxy) 3- (trifluoromethyl) phenyl] 2H-1,2,4-oxadiazin-3 (4H) -one.

 The herbicidal activity of the products of formula (I) has been demonstrated according to a methodology described below. The results show the advantage of using these products either as a total weed killer or as a selective weed killer in the pre- or post-emergence period. These products can be used as selective herbicides in cereal crops such as wheat, barley, oats, rye or maize, or in rice, soybean, cotton or sunflower crops.

 The present invention finally relates to herbicidal compositions characterized in that they contain as active ingredient, at least one of the products of formula (I) as defined above.

 The compositions according to the invention can be prepared by mixing the active ingredient with an inert filler, and thus be easily applicable by means of usual apparatus.

 It is thus possible to prepare solid compositions in powder form by grinding the active material with finely divided inert fillers such as talcs and clays, bentonite, pumice stone, fulling earth, pyrophillite, silicates, kieselguhr and other solid inert materials customarily used or by impregnating a solid support with a solution of the active ingredient followed by evaporation of the solvent.

 These solid compositions may thus be in the form of dusting powder, wettable powder or granules. The compositions according to the invention may also be in the form of a suspension, an emulsion or a solution, by mixing the active ingredient with a liquid vehicle and / or an anionic, non-ionic or non-ionic surfactant agent ensuring, among other things, uniform dispersion of the substances of compositions. The liquid vehicle may be water, alcohol, hydrocarbons or other organic solvents such as aromatic or ketonic solvents. The proportion of solvent varies from 1 to 90% depending on the solubility of the active ingredient.

 The examples and the biological study described below illustrate the invention without however limiting it.

EXAMPLE 1 4-t 4- (benzyloxy) 3- (trifluoromethyl) phenyl-5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
STAGE A: 4- (benzyloxy) 3- (trifluoromethyl) phenyl isocyanate
45 cm3 of trichloromethyl chloroformate (d = 1.64) are added to a solution of 148 g of 4- (benzyloxy) 3- (trifluoromethyl) aniline hydrochloride in 450 cm3 of dioxane with stirring under a nitrogen atmosphere. After heating for 17 hours at 50-55 ° C., the mixture is brought to dryness and thus the desired isocyanate is quantitatively obtained.

STAGE B: N '- (4- (benzyloxy) 3- (trifluoromethyl) phenyl] N-hydroxy N-methyl urea
58 g of N-methylhydroxylamine hydrochloride are mixed with 580 cm.sup.3 of dimethylformamide; the solution is stirred under nitrogen and cooled to 0 ° C. for the introduction over approximately 15 minutes of 70.8 g of triethylamine. After stirring for 1 hour at 20 ° C., the precipitate obtained is filtered off and the filtrate collected, cooled to 0 ° C. and stirred under nitrogen, is added a solution of 143 g of the isocyanate obtained in stage A in 600 cm 3 of dimethylformamide. Stirring is continued for 17 hours at 200 ° C., then the solution is poured into water and extracted with isopropyl ether, and after drying over magnesium sulphate and evaporation of the solvent, 169 g of the desired urea are obtained. , 28 (eluent: methylene chloride-tetrahydrofuran (9-1) mixture).

Infra red (CHCl 3 in cm 1) 1536: secondary amide 1669, 1690: C = O 1624, 1604, 1508: aromatic 3424: = C-NH3534: -OH
STAGE C: 4- (4- (benzyloxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
3.40 g of product prepared in Stage B are dissolved in 10 cm3 of dimethylsulfoxide; after adding 6.9 g of potassium carbonate and then 3 g of 1,2-dichloroethane (d = 1.256), the mixture is stirred under nitrogen overnight, poured into water, extracted with isopropyl ether , dried and concentrated. An oil is obtained which is chromatographed on silica eluting with toluene-ethyl acetate (9-1) and 2.3 g of the desired product are thus collected.

Microanalysis: C18H17F3N2 3 = 366.34
CHFN% calculated 59.01 4.67 15.55 7.64% found 58.9 4.7 15.7 7.4
EXAMPLE 2 4-t 4- (difluoromethoxy) 3- (trifluoromethyl) phenyl] -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
STAGE A: 5,6-Dihydro 4- [4-hydroxy-3- (trifluoromethyl) phenyl] -2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
64.6 g of the product prepared in Stage C of Example 1 are mixed with 800 cm 3 of methanol and subjected to hydrogenation in the presence of 6 g of 50% palladium-on-charcoal hydroxide. After absorption of 3.9 liters of hydrogen, the catalyst is filtered and the filtrate brought to dryness, the dry extract obtained is recrystallized from 100 cm3 of hot methanol to obtain 40.2 g of the desired product. Rf = 0.2 (eluent: mixture methylene chloride-tetrahydrofuran (95-5)).

Microanalysis: C11H11F3N2O3 = 276.217
CHFN% calculated 47.83 4.01 20.63 10.14% found 47.7 4.1 20.5 10.0
STAGE B: 4- (4- (difluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
3 g of the product prepared in the preceding stage are introduced into a solution cooled at 0 ° C. of 0.54 g of sodium hydride at 50% in oil in 5 cm 3 of dimethylformamide.

 After stirring for 0.5 hours at 20 ° C., the chlorodifluoromethane is bubbled and heated at 50 ° C. for 17 hours, the solution is then poured into an ice / normal hydrochloric acid mixture, extracted with methylene chloride and the organic phase washed. It is dried and filtered and the filtrate is brought to dryness After chromatography on silica eluting with methylene chloride-ethyl acetate (95-5) and recrystallization from pentane, 2.51 g of the desired product is obtained. = 0.4 (eluent: mixture methylene chloride-ethyl acetate (95-5)).

Microanalysis: C12H11F5N2O3 = 326.21
CHFN% calculated 44.18 3.40 29.12 8.59% found 44.0 3.4 29.5 8.5
NMR (CDCl3 250 MHz ppm) 3.22: methyl substituents at position 2 3.81: hydrogens at position 5 of the 4.33 ring: hydrogen at position 6 of the 6.51 ring: hydrogen of the difluoromethoxy radical 7.31 to 7.67: aromatic hydrogens.

EXAMPLE 3 4-C4- (bromodifluoromethol) 3- (trifluoromethyl) phenyl) 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
In a stainless steel bomb, 5 g of 50% sodium hydride in oil, 100 cm 3 of dimethylformamide and 10 cm 3 of hexamethylphosphoramide are introduced at 20 ° C. under nitrogen, then 10 g of the product prepared at the stage are added. A of Example 2, stirred for 1 hour at 20 ° C and then introduced 50 cm3 of dibromodifluoromethane.On closed the bomb and heated for 17 hours at 55-60 ° C. After cooling to 0 C the contents are poured into the normal hydrochloric acid, extracted with methylene chloride, the organic phase, washed, dried over magnesium sulphate and filtered, and the filtrate brought to dryness After chromatography on silica eluting with methylene chloride, 11.28 g of the product are collected. Rf = 0.25 (eluent methylene chloride).

Microanalysis: C12H10BrF5N2O3 = 405.126
CH Br FN% calculated 35.58 2.49 19.72 23.45 6.9% found 35.4 2.4 19.6 23.3 6.8
NMR (CDCl3 250 MHZ ppm) 3.23: methyl substituent hydrogens at position 2 3.84: hydrogen at position 5 of the 4.35 ring: hydrogen at position 6 of the ring 7.46 to 7.73: aromatic hydrogens.

EXAMPLE 4 4- [4- (1,1,2,3,3,3-Hexafluoro propoxy) 3- (trifluoromethyl) phenyl) 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
5 g of the product prepared in Stage A of Example 2 are mixed with 50 cm3 of acetonitrile and 3.8 g of potassium carbonate. The mixture is cooled to 0 ° C. and 1,1,2,3,3,3-hexafluoro-propene is bubbled for 10 to 15 minutes.

 The temperature is allowed to rise to 20-25 ° C., then poured into normal hydrochloric acid and extracted with methylene chloride, the organic phase is washed, dried, filtered and the filtrate is brought to dryness, after chromatography on silica eluting with methylene chloride gives 3.3 g of the desired product Rf = 0.25 (eluent: methylene chloride).

Microanalysis: C14H11FgN2O3 = 426.245
CHFN% calculated 39.45 2.60 40.12 6.57% found 39.5 2.5 40.2 6.6
NMR (CDCl3 250 MHz ppm) 3.22: hydrogens of the methyl substituent at the 2-position 3.82: hydrogen at the 5-position of the 4.33-ring: hydrogens at the 6-position of the 5.04-ring: hydrogen of the radical 1,1,2 3,3,3-hexafluoropropoxy, 7,21 to 7,60: aromatic hydrogens.

EXAMPLE 5: 5,6-Dihydro-2-methyl-4- [4- [1,1,3,3,3-pentafluoro-r (4-methylphenyl) sulfonyloxy) propoxy) 3- (trifluoromethyl) phenyl) 2H- 1,2,4-oxadiazin-3 (4H) -one
5 g of the product prepared in Stage A of Example 2 are mixed with 20 to 75 cm3 of acetone, 7.5 g of potassium carbonate and 17.5 g of 2,2,2-trifluoro-1-tosylate. (trifluoromethyl) ethyl. The suspension is refluxed for 5 hours, cooled and poured into water, extracted with methylene chloride, the organic phase, washed, dried and filtered and the filtrate brought to dryness. The residue is chromatographed eluting with Hexane-ethyl acetate (5-5).

After crystallization, 1.76 g of the desired product are obtained.

Rf = 0.3 (eluent: hexane).

Microanalysis: C21H18F8N2O6S = 578.437
CHFNS% calculated 43.61 3.14 26.28 4.84 5.54% found 43.60 3.0 26.1 4.8 5.8
NMR (CDCl3 250 MHz ppm) 2.44: methyl group hydrogens of the tosyl group 3.21: methyl substituents at the 2-position 3,80: hydrogens at the 5-position of the 4,32 ring: 6-position hydrogens of the 5-ring , 34: hydrogen at the 2-position of the 1,1,3,3,3-pentafluoro 2 - [(4-methylphenyl) sulfonyloxy)] propyl radical 7.35-7.82: aromatic hydrogens.

EXAMPLE 6 Ethyl 4- (2-methyl-3-oxo-3,4,5,6-tetrahydro-2H-1,2,4-oxadiazin-4-yl) -2- (trifluoromethyl) phemoxy) acetate
3 g of the product prepared in Stage A of Example 2 are mixed at 20 ° C., 50 cm 3 of acetone, 3 g of potassium carbonate and 4.17 g of ethyl bromoacetate. for 17 hours, cooled and poured into water, extracted with methylene chloride, the cyanic phase washed, dried and filtered, and the filtrate brought to dryness.

 After recrystallization from isopropyl ether, 2.83 g of the desired product are obtained. Rf = 0.2 (eluent methylene chloride-ethyl acetate (95-5)).

Microanalysis: C15H17F3N2O3 = 362.307
CHFN% calculated 49.73 4.73 15.73 7.73% found 49.6 4.7 15.5 7.6
NMR (CDCl3 250 MHz) 1.29: hydrogen at the 2-position of the ethyl radical 3.20: hydrogens of the methyl substituent at the 2-position 3.77: hydrogens at the 5-position of the 4,27-ring: hydrogen at the 1-position of the ethyl radical 4 , 31: hydrogen at position 6 of ring 4,71: hydrogen at the alpha position of carbonyl 6,89 to 7,56: aromatic hydrogens.

EXAMPLE 7 Ethyl 2-14- (2-methyl-3-oxo-3,1,5,6-tetrahydro-2-yl-1,2,4-oxadiazin-4-yl) 2- (trifluoromethyl) phemoxy] propionate
By operating in the same manner as in Example 6, replacing ethyl bromoacetate with 4.6 g of ethyl 2-bromo propionate gives 3.25 g of the desired product. Rf = 0.45 (eluent: methylene chloride-ethyl acetate (95-5)).

Microanalysis: C16H19F3N2O5 = 376.334
CHFN% calculated 51.06 5.09 15.14 7.44% found 50.9 5.1 15.0 7.3
NMR (250 MHz CDCl3) 1.25: 2-position hydrogen of the ethyl radical 1.66: hydrogen at the 2-position of the ethoxy group 3.20: hydrogen of the methyl substituent at the 2-position 3.75: hydrogen at the 5-position of the ring 4 , 22: hydrogen at position 1 of the ethyl radical 4.31: hydrogen at position 6 of the ring 4.78: hydrogen at the alpha position of the carbonyl from 6.85 to 7.54: aromatic hydrogens.

EXAMPLE 8: (4- (2-Methyl-3-oxo-3,4,5,6-tetrahydro-2H-1,2,4-oxadiazin-4-yl) -2- (trifluoromethyl) -phenoxy] -acetic acid
Refluxed for 17 hours a solution containing 6.5 g of the product prepared in Example 6, 5 cm3 of sodium hydroxide solution and 50 cm3 of absolute ethane, and then poured on an aqueous solution of hydrochloric acid at pH = 1.

 After extraction with methylene chloride, washing, drying and filtration of the organic phase, the filtrate is brought to dryness and the extract crystallizes in isopropyl ether. A product is thus obtained which, chromatographed on silica eluting with methylene chloride-acetic acid at 1% in methanol (8-2), gives 1.63 g of the desired acid. 0.28 (eluent: methylene chloride-acetic acid 1% in methanol (8-2)).

Microanalysis: C13H13F3N2 5 = 334.254
CHFN% calculated 46.71 3.92 17.05 8.38% found 46.4 3.8 17.4 8.4
EXAMPLE 9: 2- [4- (2-Methyl-3-oxo-3,4,5,6-tetrahydro-2H-1,2,4-oxadiazin-4-yl) -2- (trifluoromethyl) -propoxy] propionic acid
A solution containing 6 g of the product obtained in Example 7, 2 g of potassium hydroxide solution, 20 cm3 of ethanol and 20 cm3 of water is stirred for 3 hours at 20 ° C. and then acidified to pH = 1 with water. concentrated hydrochloric acid. After extraction of the methylene chloride, washing, drying and filtration of the organic phase, the filtrate is brought to dryness and the extract chromatographed on silica eluting with methylene chloride-acetic acid to 1 "/ ml in methanol (9-1).

3.43 g of the desired acid are collected. Rf = 0.17 (eluent methyl chloride-acetic acid at 1 ./ .. in methanol (9-1)).

Microanalysis: C14H15F3N2O5 = 348.281
CHFN% calculated 48.28 4.34 16.36 8.04% found 48.5 4.2 16.4 8.1
EXAMPLE 10: 5,6-Dihydro-2-methyl-4- [4 - [(pentafluorophenyl) methoxy) -3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazin-3 (4H) one
Refluxed for 5 hours under nitrogen a solution containing 1.4 g of the product prepared in Step A of Example 2, 0.72 cm3 of 1- (bromomethyl) 2,3,4,5,6-pentafluoro benzene 1.38 g of potassium carbonate and 40 cm3 of acetone.

After cooling, the solution is poured into 100 cm3 of water and then extracted with methylene chloride. The organic phase is washed, dried and filtered and the filtrate brought to dryness. The residue obtained is chromatographed on silica eluting with a mixture of methylene chloride-isopropyl ether (95-5) and gives 2.13 g of the desired product. Rf = 0.23.

(thin layer chromatography, support: silica, eluent methylene chloride-isopropyl ether (95-5)).

Microanalysis: C18H12F8N2 3 = 456.3
CHFN% calculated 47.4 2,65 33.3 6.1% found 47.6 2.5 31.6 6.1
EXAMPLE 11: 5,6-Dihydro-4-E4-L (3-fluoro-phenyl) -methoxy-3 (trifluoromethyl) phenyl] -2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
Working in the same manner as in Example 10, replacing 1- (bromomethyl) 2,3,4,5,6-pentafluoro benzene with 0.6 cm 3 of 1- (chloromethyl) 3-fluoro benzene and while maintaining the reflux 24 hours, 1.7 g of the desired product are obtained. Rf = 0.2 (thin layer chromatography, silica support, eluent: methylene chloride-isopropyl ether (95-5)).

Microanalysis: C18H16F4N2O3 = 384.33
CHFN% calculated 56.25 4.2 19.77 7.3 found 56.5 4 19.42 7.3
EXAMPLE 12: 5,6-Dihydro-4-E4-L (2,3-dihydro-1,4-benzodioxin-2-yl) methoxy] -3- (trifluoromethyl) phenyl] -2-methyl-1,2,4-oxadiazin-3 (4H) ) -one
A mixture containing 4.2 g of the product prepared in Stage A of Example 2, 3.45 g of 2- (bromomethyl) 2,3-dihydro-1,4-benzodioxine and 4.14 g of carbonate are prepared under nitrogen. potassium and 120 cm3 of 2-butanone; the whole is refluxed for 72 hours, then cooled and poured into 400 cm3 of water. After extraction with methylene chloride, purification by chromatography and crystallization in pentane, 1.87 g of the desired product are obtained. Rf = 0.34 (eluent methylene chloride-tetrahydrofuran (95-5)).

EXAMPLE 13 4- [4- (cyclopropylmethoxy) 3- (trifluoromethyl) phenyl) 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
A mixture containing 5.54 g of the product prepared in Stage A of Example 2, 3 g of (bromomethyl) cyclopropane, 90% and 40 cm 3 of dimethylformamide is prepared under nitrogen.

The solution is cooled to 0 ° C. and then 1 g of 50% sodium hydride in oil is added. After stirring for 4 hours at 20 ° C., the mixture is poured into water and extracted with isopropyl ether. After washing, drying, evaporation of the solvent, recrystallization in pentane, 3.9 g of desired product are obtained. Rf = 0.38 (eluent: methylene chloride-tetrahydrofuran (95-5)).

Microanalysis: C15H17F3N203 3,330.3
CHFN% calculated 54.5 5.2 17.25 8.5% found 54.5 5.1 17.1 8.3
NMR (CDCl3, ppm) 0.3 to 0.8: hydrogen in positions 2 and 3 of the cyclopropyl radical 1 to 1.5: hydrogen in position 1 of the cyclopropyl radical 3.25: hydrogens of the methyl substituent in the 2-position 3.7 at 3,9: hydrogens in position 5 of the ring 3,9: hydrogen of the methoxy radical 4,3 to 4,45: hydrogens in position 6 of the ring 7 to 7,6: aromatic hydrogens.

EXAMPLE 14: 5,6-Dihydro-2-methyl-4- (4- (2-propenyloxy) -3- (trifluoromethyl) phenyl-2H-1,2,4-oxadiazin-3 (4H) -one
Working in the same manner as in Example 13 from 5.53 g of the product prepared in Stage A of Example 2, 2.65 cm 3 of 98% alkyl bromide, 50 cm 3 of dimethylformamide, 1 g of sodium hydride at 50% in oil and without reflux, 5.66 g of the expected product is obtained. Rf = 0.45 (eluent: Methylenetetrahydro furan chloride (95-5))
PF = 61.2 C.

NMR (CDCl 3 300 MHz) 3.20: hydrogens of the methyl substituent in the 2-position 3,76: hydrogens in the 5-position of the 4,31-ring: hydrogens in the 1-position of the 2-propenyloxy radical 4,63: hydrogens in the 6-position of the ring 5.30 - 5.46 - 6.01: ethylenic hydrogens 6.98 to 7.53: aromatic hydrogens.

EXAMPLE 15: 5,6-Dihydro-2-methyl-4- [4- (3-methyl-2-butenyloxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one
By operating as in Example 14, using 3 g of isobutenyl bromide in place of the alkyl bromide and purifying the crude product by chromatography on silica eluting with methylene chloride-isopropyl ether mixture (95). -5), 4.83 g of the expected product are obtained. Rf = 0.45 (eluent: methylene chloride-tetrahydrofuran (9-1)).

Mp = 76.8-770C.

Microanalysis: C16H19F3N2O3 = 344.34
CHFN% calculated 55.8 5.56 16.55 8.13% found 55.7 5.3 16.4 7.9
NMR (CDCl3, 60 MHz, ppm) 1.72 to 1.76: Methyl hydrogens of the isobutenyloxy radical 3.2: Hydrogens of the methyl substituent at the 2-position 3.6 to 3.8: Hydrogens at the 5-position of the 4.2 ring at 4.36: hydrogens at the 6-position of the 4,5 to 4,6-ring: hydrogen at the 1-position of the isobutenyloxy-5,4,4 radical: ethylenic hydrogen 6,8 at 7,46: aromatic hydrogens.

EXAMPLE 16 4- (4- (3,3-Dichloro-2-propenyloxy) -3- (trifluoromethylphenyl) -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
Working in the same manner as in Example 15, using 3.8 g of 3,3-dichloroalkyl bromide instead of isobutenyl bromide, 5.58 g of the desired product is obtained.

Rf = 0.27 (eluent: methylene chloride - isopropyl ether (95-5)). PF = 49-50C.

EXAMPLE 17: 5,6-Dihydro-2-methyl-4-E4- (2-propynyloxy) -3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazin-3 (4H) -one
To a solution of 5.52 g of the product prepared in Stage A of Example 2, in 100 cm3 of 2-butanone, 5.52 g of potassium carbonate and 3 cm3 of propargyl bromide are added.

After 5 hours under reflux, the reaction medium is poured into 200 cm3 of water, extracted with isopropyl ether, the organic phase washed, dried and concentrated in vacuo, the oil obtained is chromatographed on silica eluting with the chloride mixture. of methylene-ethyl acetate (95-5) and gives 5.25 g of the desired product. PF = 84 C.

Microanalysis: C14H13F3N2O3 = 314.27
CHFN% calculated 53.50 4.17 18.13 8.91% found 53.6 4.2 17.9 8.9 RNN (CDCl3, ppm) 2.5: Acetylenic hydrogen 3.18: Hydrogens of the methyl substituent in position 2,67: hydrogens at the 5-position of the 4,38-ring: hydrogens at the 6-position of the 4,75-ring: hydrogen at the 1-position of the 2-propynyloxy radical 7,13-7,5: aromatic hydrogens.

EXAMPLE 18 4- [4 - [(1-Fluoro-2-iodo-ethenyl) oxy) -3- (trifluoromethyl-phenyl) -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) - one
1 g of 50% sodium hydride in oil, 20 cm 3 of dimethylformamide, 2 cm 3 of hexamethylphosphoramide and then 2 g of the product prepared in Stage A of Example 2 are introduced under argon into a metal bomb. The mixture is stirred for 1 hour at 20 ° C. and then 1.5 ml of 1,1,1-trifluoro-2-iodo ethane is added. After heating at 60 ° C. for 17 hours at a constant volume, the mixture is cooled and poured onto an ice / normal hydrochloric acid mixture, extracted with methylene chloride, dried, filtered and the filtrate is brought to dryness. After purification by chromatography on silica eluting with methylene chloride, 2.05 g of the desired product is collected. Rf = 0.25 (eluent methylene chloride).

Microanalysis: C13H11F4IN2O3 = 446.15
CHFIN Calculations 34.99 2.48 17.03 28.44 6.28% found 35 2.4 17.4 28.0 6.2
EXAMPLE 19: 5,6-Dihydro-2-methyl-4- [4- (1-phenyl-1H-tetrazol-5-yl) oxy) -3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazin-3 (4H) -one
2.77 g of the product prepared in Stage A of Example 2, 1.81 g of 5-chloro-1-phenyl 1H-tetrazol, 2.76 g of potassium carbonate and 75 cm 3 of acetone are mixed under nitrogen, the mixture is refluxed overnight, poured into water, extracted with methylene chloride, the organic phase dried, filtered and the filtrate brought to dryness. After recrystallization from ethanol, 2.75 g of the desired product is recovered.

Rf = 0.35 (eluent: methylene chloride - tetrahydrofuran (95-5)).

Microanalysis: C18H15F3N6O3 = 420.36
CHFN% calculated 51.4 3.6 13.5 20% found 51.4 3.5 13.5 19.8
Infra red (CHCl3 on Nicolet, in cm-1) 1499 - 1542 - 1619: aromatic C = C 1597: C = N 1661: C = O
EXAMPLE 20: 5,6-Dihydro-2-methyl-4- (4- (2,2,2-trifluoroethoxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one
STAGE A: 4-Fluoro-3- (trifluoromethyl) phenyl isocyanate.

A-1) Preparation of 4-fluoro-3- (trifluoromethyl) aniline hydrochloride. About 700 cm3 of a 2.8 N ethanolic solution of hydrochloric acid is added to 300 g of 4-fluoro-3- (trifluoromethyl) aniline in 2 l of isopropyl ether, brought to dryness, the residue is taken up in 2 l of dichloromethane. sulfuric ether, wring and dry the hydrochloride at 200C under vacuum.

A-2) 4-Fluoro-3- (trifluoromethyl) phenyl isocyanate.

4-Fluoro-3- (trifluoromethyl) aniline hydrochloride is dissolved under nitrogen in 2 lites of dioxane and treated with 200 cm 3 of trichloromethyl chloroformate (d = 1.64). The mixture is heated for 17 hours at 40-45 ° C. and then brought to dryness to obtain 343 g of the desired product.

STAGE B: N '- (4-Fluoro-3- (trifluoromethyl) phenyl] N-hydroxy
N-methyl urea.

A solution of 240 g of hydrochloride is prepared at 20 C
N-methyl hydroxylamine in 3 liters of chloroform and 279 g of triethylamine are added at 10 ° C. for 1 hour After stirring for 1 hour at 20 ° C., a solution of 343 g of the isocyanate above in 2 liters of chloroform After stirring for 6 hours, 4 liters of water are added and the mixture is extracted with chloroform and then with ethyl acetate.

After drying, filtration and evaporation of the solvent, the residue obtained is slurried in hexane, then drained and dried to obtain 303 g of the desired product. Rf = 0.25 (eluent: methylene chloride - tetrahydrofuran (95-5)).

3.23: hydrogens of the methyl radical 7.09 to 7.72: aromatic hydrogens 8.05: hydrogens of the radical -OH and the group -NH
STAGE C: 4- [4-Fluoro-3- (trifluoromethyl) phenyl] -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one.

 300 g of the product of the preceding stage are dissolved under nitrogen at 20 ° C. in 3 l of dimethylsulfoxide, then 1200 g of anhydrous potassium carbonate and 300 cm3 of 1,2-dichloroethane (d = 1,256) are added. The suspension is stirred for 4 hours, poured into water and extracted with isopropyl ether. After washing, drying, filtration and evaporation of the solvent, a residue is obtained which, after chromatography on silica eluting with the flugene-2-butanone mixture (8-2), gives 260 g of desired product. Rf = 0.35 (glutinous flugene-2-butanone (8-2).

NMR (CDCl 3, ppm) 3.18: hydrogen of the methyl substituent in position 2 3.63 to 3.86: hydrogen in position 5 of the 4.16 to 4.41 ring: hydrogen in position 6 of the ring 6.9 to 7.7: aromatic hydrogens.

STAGE D: 5,6-Dihydro-2-methyl-4- [4- (2,2,2-trifluoroethoxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one
1.4 cm3 of 2,2,2-trifluoroethanol (d = 1.393) are mixed with 20 cm3 of dimethylformamide and then added under nitrogen at 20-25 ° C. to a suspension of 1 g of sodium hydride at 50% in oil in 30 cm3 of dimethyl formamide, stirred for one hour at this temperature. 5 g of the product prepared in the preceding stage and 10 cm3 of dimethylformamide are then added and the mixture is then heated at 75-80 ° C. for 1.5 hours.

After cooling, it is poured on a water-ice mixture, drained, washed with water then with pentane and dried to obtain 5.6 g of the desired product. Rf = 0.38 (eluent: methylene chloride - ethyl acetate (95-5)).

Microanalysis: C13H12F6N2 3 = 358.242
CHFN% calculated 43.59 3.38 31.82 7.81% found 43.5 3.2 31.6 7.8
EXAMPLE 21: 4- [4- (2-Fluoroethoxy) 3- (trifluoromethyl) phenyl) -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
1.3 cm3 of 2-fluoroethanol (d = 1.108) are poured at -10.degree.-15.degree. C. under nitrogen into a suspension containing 1 g of 50% sodium hydride in oil in 30 cm.sup.3 of dimethylformamide; the mixture is stirred for 1 hour at 20-25 ° C., then 5 g of the product prepared in Stage C of Example 20 are added and the whole is heated for 17 hours at 60 ° to 65 ° C. The solution is then poured into the water and extracted with isopropyl ether and then with methylene chloride. The cyanic phases are washed, dried, filtered and the filtrates brought to dryness.

 The extract is recrystallized from isopropyl ether and gives 3.1 g of the desired product. Rf = 0.15 (eluent hexane - tetrahydrofuran (6-4)).

Microanalysis: C13H14F4N2O3 = 322.262
CHFN Calculations 48.45 4.38 23.58 8.69% found 48.6 4.3 23.3 8.7
NMR (CDCl 3 + DMSO: 300 MHz) 3.07: hydrogens of the methyl substituent at the 2,38 position: hydrogens at the 5-position of the 4,28-ring: hydrogens at the 6-position of the 4,39-ring: hydrogen at the 1-position of the (2-fluoroethoxy) radical 4.74: hydrogen at the 2-position of the (2-fluoroethoxy) radical 7.29 to 7.64: aromatic hydrogens.

EXAMPLE 22: 5,6-Dihydro-2-methyl-4- [4- [1- [4- (trifluoromethyl) phenyl) ethoxy) 3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazin-3 (4H) -one
4.1 g of alpha-methyl 4- (trifluoromethyl) benzyl alcohol are poured at 0 ° C. under nitrogen into a suspension containing 0.95 g of 50% sodium hydride in oil in 30 cm 3 of dimethylformamide. After stirring for 1 hour at 20-25 ° C., a solution of 5 g of the product of Step C of Example 20 is added and the mixture is stirred for 2 hours at 25 ° C. and then for 17 hours at 60 ° C. in water, extracted with isopropyl ether, washed, dried and filtered the organic phase and dry the filtrate. After chromatography on silica eluting with methylene chloride-ethyl acetate (95-5), 2.9 g of the desired product are obtained. Rf = 0.3 (eluent: methylene chloride ethyl acetate (95.degree. -5)).

Microanalysis: C20H18F6N2 3 4 448.367
CHFN% calculated 53.58 4.05 25.42 6.24% found 53.4 4.0 25.7 6.3
NMR (CDCl 3; ppm) 1.61-1.72: 2-positional hydrogens of the 1- [4- (trifluoromethyl) phenyl] ethoxy radical 3.2: hydrogens of the methyl substituent at the 3.63-3 position, 72 - 3.81: hydrogens at the 5-position of the ring 4,2 - 4,29 - 4,38: hydrogens at the 6 - position of the ring 5,27 - 5,38 - 5,49 - 5,6: hydrogens in position 1 1- [4- (4- (trifluoromethyl) phenyl] ethoxy 6-7,75: aromatic hydrogen.

EXAMPLE 23: 4- [4 - [(4-Fluoro-phenyl) -methoxy) -3- (trifluoromethyl) -phenyl) -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
Refluxed for 7.5 hours a mixture containing 3 grams of the product prepared in Step A of Example 2, 1.8 cm3 of 1- (bromomethyl) 4-fluoro benzene, 2.84 g of potassium carbonate and 22 cm3 of acetone, then poured on ice, extracted with methylene chloride, the organic phase is washed, dried, filtered and the filtrate concentrated to obtain a crude product which is impasted with isopropyl ether and thus collects 3.43 g of the desired product. Rf = 0.27 (thin layer chromatography, support: silica 60, eluent methylene chloride - isopropyl ether (95-5)).

Microanalysis: C18H16F4N2O3 = 384.335
CHFN% calculated 56.25 4.20 19.77 7.29% found 56.3 4.1 19.9 7.3
NMR (CDCl 3; ppm) 3.2: hydrogens of the methyl substituent at the 2-position 3.6 to 3.8: hydrogens at the 5-position of the 4.2 to 4.4 ring: hydrogens at the 6-position of the 5.1 ring: hydrogen at the alpha position of the 4-fluoro benzyl radical 6.9 to 7.5: aromatic hydrogens.

Using the method or its variants as illustrated by the preceding examples, the following products have also been prepared:
EXAMPLE 24 4- (4 - ((2-Fluoro-phenyl) -methoxy) -3- (trifluoromethyl) -phenyl) -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
EXAMPLE 25: 5,6-Dihydro-2-methyl-4- [4- (2,2,3,3-tetrafluoropropoxy) -3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazin-3 (4H) - one
EXAMPLE 26: 5,6-Dihydro-2-methyl-4- (4- (2,2,2-trifluoro-1-methylethoxy) -3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazine 3 (4H) - one
EXAMPLE 27 4- [4- [2- (4-Fluoro-phenyl) -ethoxy) -3- (trifluoromethyl) phenyl) -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one
Study of herbicidal activity 1) Method.

 Horticultural test plant crops containing 5 seedlings per pot in an earthy mixture of clay loam-sandy loam (75%), river sand (12.5%) and potting soil (12.5%) are treated either immediately after sowing (pre-emergence test (H)), or at the two-leaf stage of the seedling (post-emergence test (K)), by spraying a suspension of the active ingredient in a water mixture -acetone at doses of 2.5 kilograms per hectare.

 The controls in the pre-emergence tests are carried out 28 days after treatment and in post-emergence tests 21 days after treatment.

 An overall effectiveness (EF) is defined, taking into account, on the one hand, the actual mortality (MR) and, on the other hand, the weight reduction (RP) of the samples that are still alive, (MR) and (RP) being expressed as a percentage. compared to untreated controls.

MR + [(100 - MR) x RP]
EF =
100
The following table summarizes for each product, the overall efficacy calculated from the results of the tests carried out at a rate of 2.5 kg / ha on the following species - Triticum sativum (Winter Soft Wheat Variety Festival) (BTH) - Beta vulgaris (Ceres monogamous beet variety Cerès) (BE) - Brassica sp (winter rape variety Jet New) (CH) - Galium apasine (Cleavers) (G) - Chenopodium album (Goosefoot) (C) - Alopecurus myosuroïdes (Vulpin ) (V).

<Tb>

Product <SEP> of
<tb> the example <SEP> TEST <SEP> BTH <SEP> V <SEP> BE <SEP> CH <SEP> C <SEP> G
<tb><SEP> 2 <SEP> H <SEP> 50 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 95
<tb><SEP> K <SEP> 81 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100
<tb><SEP> 23 <SEP> H <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0
<tb><SEP> K <SEP> 0 <SEP> 100 <SEP> 100 <SEP> 85 <SEP> 88 <SEP> 62
<tb><SEP> 3 <SEP> H <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0
<tb><SEP> K <SEP> 0 <SEP> 99 <SEP> 0 <SEP> 100 <SEP> 75 <SEP> 75
<tb><SEP> 18 <SEP> H <SEP> 0 <SEP> 40 <SEP> 80 <SEP> 100 <SEP> 0 <SEP> 25
<tb><SEP> K <SEP> 0 <SEP> 0 <SEP> 100 <SEP> 100 <SEP> 25 <SEP> 100
<tb><SEP> 20 <SEP> H <SEP> 62 <SEP> 94 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100
<tb><SEP> K <SEP> 55 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 50 <SEP> 100
<tb><SEP> 15 <SEP> H <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0
<tb><SEP> K <SEP> 0 <SEP> 10 <SEP> 100 <SEP> 100 <SEP> 0 <SEP> 10
<Tb>

<tb><SEP> 16 <SEP> H <SEP> 0 <SEP> 99 <SEP> 95 <SEP> 100 <SEP> 100 <SEP> 25
<tb><SEP> K <SEP> 75 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 88 <SEP> 100
<tb><SEP> H <SEP> 50 <SEP> 94 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 99
<tb> 14
<tb><SEP> K <SEP> 100 <SEP> 30 <SEP> 0 <SEP> 100 <SEP> 62 <SEP> 100
<tb><SEP> H <SEP> 25 <SEP> 98 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 95
<tb> 13
<tb><SEP> K <SEP> 25 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 62 <SEP> 100
<tb><SEP> 17 <SEP> H <SEP> 92 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100
<tb><SEP> K <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100 <SEP> 100
<Tb>
These results clearly show the advantage of using the products of formula (I) as herbicides and especially those of Examples 2, 13, 14, 16, 17 and 20.

 The dose of 2.5 kilograms per hectare of use of the products of formula (I) is not limiting and according to the crop, the state of the soil, the climatic conditions and the method of spreading, can vary from 0, 1 to 10 kilograms per hectare.

EXAMPLE 28 Emulsifiable concentrate according to the invention
A composition containing by weight 15% of product of Example 16, 6.4% of atlox 4851 (oxyethylene triglyceride combined with a sulfonate, acid number 1.5) was prepared. 3.2% of atlox 4855 (oxyethylene triglyceride combined with a sulfonate, acid number 3) and 75.4% xylene.

EXAMPLE 29 Wettable Powder According to the Invention
A wettable powder containing 25% of compound of Example 13, 15% of ekapersol (condensation product of sodium naphthalene sulphonate, 0.5% of brecolane) was prepared.
NVA (sodium alkyl naphthalene sulfonate) 34.5% zeozil 39 (synthetic hydrated silica precipitated) and 25% vercoryl "S" (colloidal kaolin).

Claims (15)

1) The products of formula (I)

 in which R represents a cyclic or acyclic radical, saturated or unsaturated, substituted or unsubstituted, containing from one to fourteen carbon atoms and optionally from one to four identical or different heteroatoms, it being understood that R can not represent an acyclic hydrocarbon radical; , saturated and unsubstituted having one to four carbon atoms. 2) The products defined according to claim 1 and having the formula (I1)

 in which R 1 represents a saturated or unsaturated, linear or branched, acyclic hydrocarbon radical containing from one to four carbon atoms and substituted by one or more radicals chosen from halogen atoms, alkyloxy radicals containing from one to four carbon atoms; carboxy, alkoxycarbonyl containing from two to five carbon atoms, toxyloxy, mesyloxy, cycloalkyl containing from three to six carbon atoms or phenyl optionally substituted with one or more halogen atoms. 3) The products defined according to any one of claims 1 or 2 corresponding to the formula (I2)

 wherein R2 represents an alkyl radical having one to three carbon atoms substituted with one or more fluorine atoms and optionally a chlorine or bromine atom. 4) The products defined according to any one of claims 1 or 2 answering the formula (I3)

 wherein R3 represents an alkenyl or alkynyl radical containing from two to four carbon atoms and optionally substituted with one or more halogen atoms. 5) The products defined according to any one of claims 1 or 2, corresponding to formula (I4)

 in which R4 represents a radical

 in which R5 represents a hydrogen atom or a methyl radical, n is equal to 1 or 2 and m takes one of the values from 0 to 5. 6) The products as defined in any one of claims 1 to 5 and whose names follow - 4- [4- (difluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6dihydro-2-methyl-2H-1,2 4-oxadiazin-3 (4H) -one - 5,6-dihydro-4- [4 - [(4-fluoro-phenyl) -methoxy] -3- (trifluoromethyl) -phenyl] -2-methyl-1,2,4-diol oxadiazin-3 (4H) -one - 4- [4- (bromodifluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one - 4- [4- (1-Fluoro-2-iodo-ethenyl) oxy) -3- (trifluoromethyl) phenyl] -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one -5 6-Dihydro-2-methyl-4- [4- (2,2,2-trifluoroethoxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one -5,6- dihydro-2-methyl-4- [4- (3-methyl-2-butenyloxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one-4- [4- (3, 3-dichloro-2-propenyloxy) 3- (trifluoromethyl) phenyl 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one -5,6-dihydro-2-methyl-4- [4-dichloro-2-propenyloxy] - (2-propenyloxy) 3- (trifluoromethyl) phenyl] 2H-1,2, 4-oxadiazin-3 (4H) -one 4- [4- (cyclopropylmethoxy) -3- (trifluoromethyl) phenyl] -5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one-5, 6-Dihydro-2-methyl-4- [4- (2-propynyloxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one. 7) Process for the preparation of the products of formula (I) as defined in claim 1 characterized in that the amine of formula (II)

 in the form of an inorganic or organic acid salt is converted into isocyanate of formula (III)

 which, treated in the presence of a base with an N-methyl hydroxylamine salt of formula (IV):  CH3-NH-OH (IV) gives the derivative of urea of formula (V)

 product of formula (V) which is reacted in the presence of a base and preferably in a polar solvent, with a 1,2-dihalo ethane of formula (VI)  X-CH 2 -CH 2 -X (VI) wherein X represents a chlorine or bromine atom, to obtain the product of formula (I). 8) variant of the process according to claim 7, characterized in that the product of formula (I4a):

 is subjected to a catalytic hydrogenation and leads to the product of formula (VII)

  that is converted in the presence of a base and by action of an etherification reagent phenols in a product of formula (I). 9) variant of the process according to claim 7, characterized in that the amine of formula (VIII)

 in the form of a salt of mineral or organic acid is converted into isocyanate of formula (IX)

 which, treated with an N-methyl hydroxylamine salt of formula (IV), gives the urea derivative of formula (X)

 product of formula (X) which is reacted in the presence of a base and preferably in a polar solvent with a 1,2-dihaloethane of formula (VI) to obtain the product of formula (XI)

 that is converted into product of formula (I) by the action of an alkali metal alcoholate prepared from the alcohol of formula (XII)  R-OH (XII) with an alkaline hydride. 10) Use as herbicides of the products of formula (I) as defined in claim 1. 11. The use as herbicides of the products of formula (I) as defined in any one of claims 2 to 5. 12) Use as herbicides of the products of formula (I) whose names follow - 4- [4- (difluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one - 5,6-dihydro 4-t4 - [(4-fluoro-phenyl) methoxy] -3- (trifluoromethyl) phenyl] -2-methyl-2H-1,2,4-oxadiazin-3 (4H) - one - 4- [4- (bromodifluoromethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one - the 4- [4- [ (1-Fluoro-2-iodo ethenyl) oxy] 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one -5,6-dihydro-2- methyl 4- [4- (2,2,2-trifluoroethoxy) -3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazin-3 (4H) -one -5,6-dihydro-2-methyl-4- 4- (3-methyl-2-butenyloxy) -3- (trifluoromethyl) phenyl) -2H-1,2,4-oxadiazin-3 (4H) -one - 4- [4- (3,3-dichloro-2-propenyloxy) 3 - (Trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one-5,6-dihydro-2-methyl-4- [4- (2-propenyloxy) 3 - (trifluoromethyl) phenyl] 2H-1,2,4-oxadiazin-3 (4H) -on e - 4- [4- (cyclopropylmethoxy) 3- (trifluoromethyl) phenyl] 5,6-dihydro-2-methyl-2H-1,2,4-oxadiazin-3 (4H) -one -5,6-dihydro-2-methyl-4- [4- (2-propynyloxy) -3- (trifluoromethyl) phenyl] -2H-1,2,4-oxadiazin-3 (4H) -one. 13) Herbicidal compositions characterized in that they contain as active ingredient, at least one of the products of formula (I) as defined in any one of claims 1 to 5. 14) Compositions according to claim 13 characterized in that they contain at least one of the products as defined in claim 6. 15) The intermediate products of the process and its variants as defined in claims 7 to 9, corresponding to formulas (III), (V), (VII), (IX), (X) and (XI).