EP0000681B1 - Amino-2 (or -4) alkylthio-5 pyrimidines, processes for their preparation, their use as herbicides and composition containing them - Google Patents

Description

The present invention relates to novel 5-alkylthio-pyrimidines carrying an amino or acylamino group, their methods of preparation and their application as herbicides.

Herbicide pyrimidine derivatives are already known (see for example French patents 2,031,422, 2,317,291, 2,119,234 and 2,137,933), but these derivatives never simultaneously carry an alkylthio group in position 5 and a group amino or acylamino.

dans laquelle R₁ est un groupe alkyle ayant 1 à 5 atomes de carbone, X₁ est un atome de chlore, X₂ est un qroupe

dans lequel R₂ est un atome d'hydrogène ou un groupe alkyle ayant 1 à 5 atomes de carbone, R₃ est un atome d'hydrogène ou un groupe alkyle ayant 1 à 5 atomes de carbone et peut être en outre, lorsque R₂ est un atome d'hydrogène, un groupe

dans lequel R est un atome d'hydrogène ou un groupe alkyle de 1 à 5 atomes de carbone, X₃ est un groupe

dans lequel R₄ est un atome d'hydrogène et R₅ est un atome d'hydrogène ou un groupe

R étant tel que défini ci-dessus.The new 5-alkylthio pyrimidines according to the invention can be represented by the general formula:

in which R ₁ is an alkyl group having 1 to 5 carbon atoms, X ₁ is a chlorine atom, X ₂ is a group

wherein R ₂ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, R ₃ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms and may be further, when R ₂ is a hydrogen atom, a group

in which R is a hydrogen atom or an alkyl group of 1 to 5 carbon atoms, X ₃ is a group

wherein R ₄ is a hydrogen atom and R ₅ is a hydrogen atom or a group

R being as defined above.

peuvent être préparés par condensation d'une trichloro-2,4,6 alkylthio-5 pyrimidine de formule (II), dans laquelle X est un atome de chlore et R₁ est un groupe alkyle ayant 1 à 5 atomes de carbone, avec un composé de formule (III), dans laquelle R₂ et R₃ ont les mêmes significations que dans la formule (I) excepté la signification

et condensation de la dichloro-4,6 alkylthio-5 pyrimidine de formule (IV) ainsi obtenue avec un composé de formule (V), dans laquelle R₄ et R₅ ont les mêmes significations que dans la formule (l) excepté la signification

The compounds of formula (I) in which R ₃ and R ₅ are not

may be prepared by condensation of a 2,4,6,6-alkylthio-pyrimidine trichloro of formula (II), in which X is a chlorine atom and R ₁ is an alkyl group having 1 to 5 carbon atoms, with a compound of formula (III), in which R ₂ and R ₃ have the same meanings as in formula (I) except the meaning

and condensation of the 4,6-dichloro-5-alkylthio pyrimidine of formula (IV) thus obtained with a compound of formula (V), in which R ₄ and R ₅ have the same meanings as in formula (l) except the meaning

The entire reaction process can be diagrammed as follows:

In the above reactions, m and n are numbers greater than O and less than 1.

The 2,4,4,6-trichloro-5-alkylthio pyrimidines of formula (II) are known products. They can be prepared for example by the process described in French patent 1,549,494 applied for on October 31, 1967.

The condensation reactions (1), (2) and (2) bis can be carried out either in an aqueous medium, or in an organic solvent medium, or even in a mixed water + organic solvent medium. As organic solvents which can be used, mention may in particular be made, without being limiting, of toluene, methanol, aliphatic ketones such as acetone, methyl ethyl ketone or diethyl ketone, dimethylformamide or an excess of compound (III), when the latter this is an amine.

The condensation reactions (1), (2) and (2) bis are carried out in the presence of a basic agent capable of fixing the hydrochloric acid HX formed in the reaction. As basic agents which can be used, there may be mentioned, for example, alkali metal hydroxides, ammonia, or an excess of the compounds of formula (III) or (V).

Reactions (1), (2) and (2) bis are carried out at a temperature which depends in particular on the solvent used. In general, reaction (1) is carried out between 0 and 150 ° C. It can therefore be carried out at a temperature lower than the ordinary temperature, for example between 0 and 10 ° C., or at a temperature higher than the ordinary temperature, for example between 100 and 150 ° C. Reactions (2) and (2) bis cannot be carried out at temperatures as low as those which can be used for reaction (1). They are generally carried out between 100 and 150 ° C. Depending on the temperature and the solvent used, reactions (1), (2) and (2) bis are carried out at atmospheric pressure or under a pressure higher than atmospheric pressure.

The 5-dichloroalkylthio pyrimidines (IV) and (IV) bis isomers obtained in reaction (1) can be separated, for example by fractional crystallization. The isomers thus separated then provide, by reactions (2) and (2) bis, the pure compound (I) and the mixture of the two compounds (I) bis and (I) ter, isomers of the compound (I).

The mixture of compounds (IV) and (IV) bis obtained in reaction (1) can also be subjected to the second stage of the process [reaction with compound (V) J. A mixture of the three isomeric compounds (I), (I) bis and (I) ter is then obtained, a mixture which can be used as it is in applications herbicides. The isomeric compounds (I), (I) bis and (I) ter can also be separated by preparative liquid chromatography.

Dans ce mélange l'isomère (VI) est prépondérant (a inférieur à 1 et supérieur à 0,5).In the case where the compounds (III) and (V) are identical and are therefore both ammonia, the isomers (I) and (I) bis are identical and the whole of the preceding reaction scheme therefore leads to two isomers [isomers of formulas (VI) and (VII) below]. In the same case, and provided that the operation is carried out at a sufficiently high temperature (100 to 150 ° C. in practice), it is possible to obtain, in a single step, from 2,4,4,6-trichloro-5-alkylthio-pyrimidine. formula (II), a mixture of isomers (VI) and (VII), according to the reaction:

In this mixture the isomer (VI) is predominant (a less than 1 and greater than 0.5).

dans lequel R₂ et R₃ sont des groupes alkyle identiques R' peuvent aussi être préparés par réaction d'une trichloro-2,4,6 alkylthio-5 pyrimidine de formule (II) avec une amine tertiaire de formule (VIII) et condensation de la dichloro-4,6 alkylthio-5 pyrimidine de formule (IX) ainsi obtenue avec l'ammoniac, suivant le schéma réactionnel suivant:

The compounds of formula (I) in which X ₃ is an NH ₂ group and X ₂ is a group

in which R ₂ and R ₃ are identical alkyl groups R ′ can also be prepared by reaction of a 2,4,4,6-alkylthio-pyrimidine trichloro of formula (II) with a tertiary amine of formula (VIII) and condensation 4,6-dichloro-5-alkylthio-pyrimidine of formula (IX) thus obtained with ammonia, according to the following reaction scheme:

Reaction (4), which has the originality of selectively providing the 4,6-dichloro-5-alkylthio-pyrimidine isomer, can be carried out in an organic solvent medium, at a temperature between 100 and 150 ° C. As organic solvents which can be used, mention may be made of the same solvents as for reactions (1), (2) and (2) bis.

Reaction (5) is carried out under the same conditions as reaction (2).

The compounds formed in reactions (1), (2), (2) bis, (3), (4) and (5) can be isolated from the reaction medium by hunting methods such as, for example, filtration, when the compounds precipitate, or the distillation under reduced pressure of the solvent followed by washing the residue with water, and purified by recrystallization from an appropriate solvent.

peuvent être préparés par acylation des composés de formule (I) dans lesquels R₃ et R₅ ne sont pas

Cette acylation est effectuée à l'aide des agents d'acylation habituels tels que chlorures d'acide, anhydrides d'acide, cétène ou composés homologues. On opère en milieu solvant organique, à une température comprise entre 20 et 120°C, de préférence entre 50 et 100°C. Comme solvants organiques utilisables on peut citer en particulier les acides carboxyliques, dans le cas où on effectue l'acylation avec un anhydride d'acide, et la pyridine, dans le cas où on effectue l'acylation avec un chlorure d'acide.The compounds of formula (I) in which at least one of the substituents R ₃ and R _s is a group

can be prepared by acylation of the compounds of formula (I) in which R ₃ and R ₅ are not

This acylation is carried out using the usual acylating agents such as acid chlorides, acid anhydrides, ketene or homologous compounds. The operation is carried out in an organic solvent medium, at a temperature between 20 and 120 ° C., preferably between 50 and 100 ° C. As organic solvents which can be used, mention may in particular be made of carboxylic acids, in the case where the acylation is carried out with an acid anhydride, and pyridine, in the case where the acylation is carried out with an acid chloride.

The compounds of formula (I) can be transformed into their salts with mineral or organic acids by reaction with the corresponding acid in an appropriate solvent.

The compounds of formula (I) and their salts with mineral or organic acids have the property of destroying a large number of undesirable plants belonging to the classes of monocotyledons or dicotyledons and this at very low doses of between 150 g / ha and 2500 g / ha. In particular they totally destroy the following plants: ryegrass, panic, crabgrass, foxtail, wild oats, bedstraw, amaranth, knotweed, capsella, speedwell, mustard, datura, chickweed, stellar, thistle, fumitory, chenopoda, sorrel, plantain , atriplex, dandelion, poppy, chrysanthemum, seneçon, milkweed, spurge. In addition, at the doses at which they are active against undesirable plants, the compounds of formula (I) and their salts generally have no unfavorable action on winter and spring cereals such as wheat and barley, on rice and corn.

The compounds of formula (I) and their salts are active with regard to adventitious plants as well in pre-emergence treatments as in post-emergence treatments. However, their activity is more marked in post-emergence treatments.

For their implementation, the herbicidal compounds according to the invention can be incorporated, jointly with other herbicides or separately, in formulations which contain, in addition to the active material, the inert additives usually used in agriculture to facilitate conservation, aqueous suspension, adhesion to foliage and resistance to atmospheric agents and biological degradation (hence greater persistence of the action), such as solid diluents (talc, silica, kieselguhr, clay, etc.). ..) or liquids (mineral oils, water, organic solvents such as ketones, alcohols, hydrocarbons or their chlorine derivatives), adjuvants, surfactants, antioxidants and stabilizers. Such formulations can be in the form of wettable powders, solutions emulsifiable in water, suspensions, granules or any other form in use in the field of herbicides.

In formulations containing only herbicidal compounds according to the invention and inert additives, the content of compounds of formula (I) or their salts (active material) can vary from 1% to 95% by weight. In the formulations containing herbicidal compounds according to the invention, other herbicides and inert additives, the content of compounds according to the invention can vary from 1% to 80% by weight, that in other herbicides from 80% to 1% by weight, the complement to 100% being constituted by inert additives.

As other herbicides which can be combined in the formulations with the compounds according to the invention, mention may be made of (3,4-dichloro-phenyl) -3 dimethyl-1,1 urea (diuron), 3-phenyl dimethyl-1,1 urea (fenuron), (3-chloro-4-methylphenyl) -3 dimethyl-1,1 urea (chlortoluron), ((chloro-4 phenyl) -3 dimethyl-1,1 urea (monuron), monolinuron, ( dichloro-3,4-phenyl) -3 methoxy-1 methyl-1 urea (linuron), isoproturon, mithabenzthiazuron, (dichloro-3,4 phenyl) -3 n-butyl-1 methyl-1 urea (neburon) , 2-chloro-ethylamino-4 isopropylamino-6 triazine-1,3,5 (atrazine), chloro-2 bis (ethylamino) -4,6 triazine-1,3,5 (simazine), amino-3 triazole-1,2,4, terbutryne, cyanazine, 2,6-diethyl N-chloroacetyl N-methoxymethyl aniline (alachlor), N-chloroacetyl N-isopropyl aniline (propachlor), napropamide, diquat, paraquat, 2,4-dichloro-phenoxyacetic acid (2,4-D), (2-methyl-4-chloro-phenoxy) -2 propionic acid (MCPP), 2-methoxy-3,6-dichloro-benzoic acid (say amba), 4-amino-3,5,6-trichloro-picolinic acid (picloram), 2,4-dinitro-6-sec-butyl-phenol (dinoseb), 4,6-dinitro-ortho-cresol (DNOC), N-(3-chloro-phenyl) 4-chloro-2-butynyl carbamate (barban), propham, terbacil, bromo-5 sec-butyl-3 methyl-6 uracil (bromacile), pyrazone, phenmedipham and the metamitron.

The following examples illustrate the invention without limiting it.

Example 1. 4-amino-6-chloro-2-ethylamino-5-methylthio pyrimidine.

The preparation of this compound is carried out in 2 stages.

• Dans un réacteur de 250 ml muni d'une agitation, on introduit 45,9 g de trichloro-2,4,6 méthylthio-5 pyrimidine, 150 g de méthyléthylcétone et 130 g d'eau. Dans ce mélange maintenu à 5°C, on ajoute en 30 minutes 9,44 g d'éthylamine en solution aqueuse à 32,5%. On maintient 1 h30 à 5°C. On ajoute ensuite 8,08 g de soude en solution aqueuse à 30%. On maintient le mélange 4 heures à 20°C et une nuit au réfrigérateur à environ 0°C. Il apparait un précipité qui est isolé par filtration, lavé avec 16 ml de méthyléthylcétone et recristallisé deux fois dans 180 ml d'éthanol. On obtient ainsi 10,5 g d'éthylamino-2 dichloro-4,6 méthyl-thio-5 pyrimidine, qui fond à 147°C et qui est identifiée par son spectre dans l'infra-rouge (IR) et son spectre de résonance magnétique nucléaire (R.M.N.)

1st step:

• 45.9 g of 2,4,6-trichloro-5-methylthio pyrimidine, 150 g of methyl ethyl ketone and 130 g of water are introduced into a 250 ml reactor equipped with stirring. To this mixture maintained at 5 ° C., 9.44 g of ethylamine in 32.5% aqueous solution are added over 30 minutes. One hour and a half is maintained at 5 ° C. 8.08 g of sodium hydroxide in 30% aqueous solution is then added. The mixture is kept for 4 hours at 20 ° C. and overnight in the refrigerator at approximately 0 ° C. A precipitate appears which is isolated by filtration, washed with 16 ml of methyl ethyl ketone and recrystallized twice from 180 ml of ethanol. 10.5 g of 2-ethylamino-4,6-dichloro-5-methyl-thio-pyrimidine are thus obtained, which melts at 147 ° C. and which is identified by its spectrum in infrared (IR) and its spectrum. nuclear magnetic resonance (NMR)

The filtrate is evaporated. 36.5 g of a mixture of 2-ethylamino-4,6-dichloro-5-methylthio-pyrimidine and of 4-ethylamino-2,6-dichloro-5-methylthio-5-pyrimidine are thus obtained, a mixture which melts at 76 ° C. is identified by its IR and NMR spectra

• Dans un autoclave de 500 ml, on introduit 7,5 g d'éthylamino-2 dichloro-4,6 méthylthio-5 pyrimidine obtenue comme indiqué ci-dessus, 110 ml de méthanol et 11 g d'ammoniac. Le mélange est chauffé à 110°C pendant 2 heures puis refroidi. On concentre sous pression réduite la solution obtenue et lave à l'eau le résidu. On obtient ainsi 8,2 g d'amino-4 chloro-6 éthylamino-2 méthylthio-5 pyrimidine, qui est identifiée par ses spectres I.R. et R.M.N. et qui fond à 124°C.

2nd step:

• 7.5 g of 2-ethylamino-4,6-dichloro-5-methylthio-pyrimidine obtained as indicated above, 110 ml of methanol and 11 g of ammonia are introduced into a 500 ml autoclave. The mixture is heated at 110 ° C for 2 hours and then cooled. The solution obtained is concentrated under reduced pressure and the residue is washed with water. 8.2 g of 4-amino-6-chloro-2-ethylamino-5-methylthio-pyrimidine are thus obtained, which is identified by its IR and NMR spectra and which melts at 124 ° C.

Example 2.

Mixture of the three isomers of 4-amino-6-chloro-2-ethylamino-5-methylthio pyrimidine, 2-amino-6-chloro-4-ethylamino-5-methylthio-pyrimidine and 2-chloro-6-amino 4-ethylamino-5-pyrimidine.

2.5 g of 2-ethylamino-4,6-dichloro-5-methylthio-pyrimidine, 9 g of the mixture of 2-ethylamino-4,6-dichloro-5,6-methylthio-5-pyrimidine and ethylamino are introduced into a 500 ml autoclave -4 2,6-dichloro-5-methylthio-pyrimidine obtained in the first step of Example 1, 165 g of methanol and 16 g of ammonia. The mixture is heated for 2 hours at 120 ° C. and then cooled. The solution obtained is concentrated under reduced pressure and the residue is washed with water. 8.2 g of a mixture melting at 76 ° C. are thus obtained. Analysis of this mixture by gas chromatography and mass spectrometry shows that it contains 56.6% 2-amino-6 chloro-4 ethylamino-5 methylthio pyrimidine, 37.8% amino-4 ethylamino -2 chloro-6 methylthio-5 pyrimidine and 5.6% amino-6 ethylamino-4 chloro-2 methylthio-5 pyrimidine.

Example 3.

Mixture of the three isomers of 2-amino-6-chloro-4-isopropylamino-5-methylthio pyrimidine, 4-amino-6-chloro-isopropylamino-2-5-methylthio-pyrimidine and 6-amino isopropylamino-4-chloro-2 methylthio-5 pyrimidine.

The synthesis is carried out in 2 steps.

• On opère comme dans la première étape de l'exemple 1 en remplaçant l'éthylamine par 11,8 g d'isopropylamine. Par évaporation sous pression réduite de la solution finale, lavage à l'eau du résidu et séchage sous pression réduite, on obtient 51,4 g d'une pâte constituée par un mélange de dichloro-4,6 isopropylamino-2 méthylthio-5 pyrimidine et de dichloro-2,6 isopropylamino-4 méthylthio-5 pyrimidine.

1st step:

• The procedure is as in the first step of Example 1, replacing the ethylamine with 11.8 g of isopropylamine. By evaporation under reduced pressure of the final solution, washing the residue with water and drying under reduced pressure, 51.4 g of a paste is obtained, consisting of a mixture of 4,6-dichloro-2-isopropylamino-5-methylthio-pyrimidine and 2,6-dichloro-4-isopropylamino-5-methylthio pyrimidine.

• Dans un autoclave de 500 ml, on introduit 12,5 g du mélange obtenu a la première étape, 250 g de méthanol et 25 g d'ammoniac. Après 2 heurs de chauffage à 130°C, on concentre sous vide la solution obtenue et lave à l'eau le résidu. On obtient ainsi 12,1 g d'un produit pâteux qui, ainsi que le montrent la chromatographie en phase gazeuse et la spectrométrie de masse, est un mélange contenant 55,1% d'amino-2 chloro-6 isopropylamino-4 méthylthio-5 pyrimidine, 39,4% d'amino-4 chloro-6 isopropylamino-2 méthylthio-5 pyrimidine et 5,5% d'isopropylamino-4 amino-6 chloro-2 méthylthio-5 pyrimidine.

2nd step:

• 12.5 g of the mixture obtained in the first step, 250 g of methanol and 25 g of ammonia are introduced into a 500 ml autoclave. After 2 hours of heating to 130 ° C., the solution obtained is concentrated under vacuum and the residue is washed with water. 12.1 g of a pasty product are thus obtained which, as shown by gas chromatography and mass spectrometry, is a mixture containing 55.1% 2-amino-6-chloro-4-isopropylamino-methylthio- 5 pyrimidine, 39.4% 4-amino-6-chloro-2-isopropylamino-5-methylthio pyrimidine and 5.5% 4-isopropylamino-6-amino-2-chloro-5-methylthio-pyrimidine.

Example 4.

Mixture of the three isomers 2-amino-6 chloro-4-methylamino-5-methylthio pyrimidine, 4-amino chloro-6-methylamino-2-methylthio-5 pyrimidine and 6-amino 2-chloro-4-methylamino-5 pyrimidine.

The synthesis is carried out in two stages.

• On opère comme dans la première étape de l'exemple 1 en remplaçant l'éthylamine par 6,2 g de méthylamine en solution à 30, 7% dans l'eau. Après réaction, on obtient par filtration 13 g d'un précipité constitué de dichloro-4,6 méthylamino-2 méthylthio-5 pyrimidine de point de fusion 142°C.

1st step:

• The procedure is as in the first step of Example 1, replacing the ethylamine with 6.2 g of methylamine in 30.7% solution in water. After reaction, 13 g of a precipitate consisting of 4,6-dichloro-2-methylamino-5-methylthio-pyrimidine with a melting point of 142 ° C. are obtained by filtration.

By concentrating the filtrate under reduced pressure and washing the residue with water, 33.4 g of a product melting at 91 ° C. are obtained which, as the IR and NMR spectra show, is a mixture of 4-dichloro , 6 methylamino-2 methylthio-5 pyrimidine and dichloro-2,6 methylamino-4 methylthio-5 pyrimidine.

• Dans un autoclave de 500 ml, on introduit 8 g de dichloro-4,6 méthylamino-2 méthylthio-5 pyrimidine, 20,6 g du mélange des deux isomères obtenu à la 1 ère étape, 50 g d'ammoniac et 350 g de méthanol. Après deux heures de chauffage à 130°C, on concentre sous vide la solution obtenue et lave à l'eau le résidu. On obtient ainsi 20,6 g d'un mélange fondant à 118°C Comme le montrent la chromatographie en phase gazeuse et la spectrométrie de masse, ce mélange contient 50,3% d'amino-2 méthylamino-4 chloro-6 méthylthio-5 pyrimidine, 48,3% d'amino-4 méthylamino-2 chloro-6 méthylthio-5 pyrimidine et 1,4% d'amino-6 méthylamino-4 chloro-2 méthylthio-5 pyrimidine.

2nd step:

• 8 g of 4,6-dichloro-2-methylamino-5-methylthio-pyrimidine, 20.6 g of the mixture of the two isomers obtained in the 1st step, 50 g of ammonia and 350 g of are introduced into a 500 ml autoclave. methanol. After two hours of heating to 130 ° C., the solution obtained is concentrated under vacuum and the residue is washed with water. This gives 20.6 g of a mixture melting at 118 ° C. As shown by gas chromatography and mass spectrometry, this mixture contains 50.3% 2-amino-4-methylamino-6 chloro-methylthio- 5 pyrimidine, 48.3% 4-amino-2-methylamino-6-chloro-5-methylthio pyrimidine and 1.4% 4-amino-methylamino-4-chloro-2-methylthio-5 pyrimidine.

Example 5.

Chloro-6 diamino-2,4 ethylthio-5 pyrimidine. A mixture of 24.6 g of barbituric acid, 20 g of diethyl sulfoxide, 75 ml of glacial acetic acid and 28 ml of acetic anhydride is heated at 95 ° C. for 5 h 30 min. After cooling, 175 ml of water are added cold. The precipitate obtained is filtered, washed with acetone and dried under reduced pressure. 21.7 g of 5-diethylsulfonium barbiturylide are thus obtained.

To the 21.7 g of 5-diethylsulfonium barbiturylide, 84.4 g of phosphorus oxychloride, 5 ml of dimethylaniline are added and the mixture obtained is heated to the boil for 20 hours. After cooling to 60 ° C., the reaction mixture is poured onto ice and stirred for 1 hour. The precipitate obtained is filtered, dried and recrystallized from hexane. 10 g of trichloro-2,4,6-ethylthio-pyrimidine with a melting point of 62-64 ° C. are thus obtained.

10 g of 2,4,4,6-trichloro-ethylthio pyrimidine, 17 g of ammonia and 100 g of methanol are introduced into a 500 ml autoclave. After 2 hours of reaction at 100 ° C., the precipitate obtained is filtered, washed with water and dried under reduced pressure. This gives 5.6 g of a product melting at 182 ° C and consisting essentially of 6-chloro-2,4-diamino-5-ethylthio-pyrimidine. This product is characterized by its I.R., R.M.N. and mass.

Example 6.

Chloro-6 diamino-2,4 butylthio-5 pyrimidine. In a 500 ml autoclave, the mixture is heated to 100 ° C. for 2 hours, 120 g of methanol, 20 g of ammonia and 17 g of 2,4,4,6-trichloro-5-butylthio-pyrimidine. After cooling, the solution obtained is concentrated under reduced pressure. The residue obtained is washed with water and recrystallized from propanol. 7 g of a product are thus obtained, melting at 129 ° C. and consisting essentially of 6-chloro-2,4-diamino-5-butylthio-pyrimidine. This product is characterized by its I.R., R.M.N. and mass.

The 2,4,4,6-butylthio-pyrimidine trichloro used as starting material is prepared according to the process described in Example 5 for the preparation of the 2,4,4,6-ethylthio-pyrimidine trichloro, initially replacing the diethylsulfoxide with dibutylsulfoxide.

Example 7.

Mixture of chloro-6 diamino-2,4-methylthio-5 pyrimidine (isomer A) and chloro-diamino-4,6 methylthio-5 pyrimidine (isomer B).

2.5 liters of methanol, 250 g of ammonia and 250 g of 2,4,4,6-methylthio-pyrimidine trichloro are introduced into a 5 liter autoclave. The mixture is heated at 100 ° C. for 2 hours and the solution obtained is concentrated under reduced pressure. Ether is added to the residue obtained. The part insoluble in ether is separated, washed with water and dried. 153.7 g of a mixture of isomers A and B are thus obtained, in which isomer A is predominant. This mixture melts at 154 ° C and is characterized by its I.R. and R.M.N.

Example 8.

4-amino-6-chloro-2-diethylamino-5-methylthio pyrimidine.

In a 500 ml flask of a condenser, 100 g of toluene, 23 g of 2,4,4,6-methylthio-pyrimidine and 10.1 g of triethylamine are heated to boiling for 3 hours. By concentration under reduced pressure of the solution obtained, a residue is obtained which is introduced into a 500 ml autoclave with 350 ml of methanol and 50 g of ammonia. The solution obtained after 2 hours of reaction at 130 ° C. is concentrated again under reduced pressure. A residue is obtained which is washed with water and which is recrystallized from a water-alcohol mixture. 17.5 g of 4-amino-6-chloro-2 diethylamino-5-methylthio-pyrimidine are thus obtained, with a melting point of 68 ° C., which is characterized by its I.R. and R.M.N.

Example 9.

Methylamino-2 amino-4 chloro-6 methylthio-5 pyrimidine.

This compound is obtained according to the procedure of Example 1, replacing in the first step the ethylamine with methylamine. It melts at 205 ° C and is characterized by its I.R. and R.M.N.

Example 10.

Acetylamino-4 diethylamino-2 chloro-6 methylthio-5 pyrimidine.

250 ml of acetic acid and 25 g of 4-amino-6-chloro-2-methylthio-5-pyrimidine prepared as indicated in a 500 ml flask equipped with a condenser and a stirrer in Example 8. The mixture is heated to 50 ° C. Then 50 ml of acetic anhydride are gradually introduced. After which it is heated for 30 minutes at reflux. Then evaporated in vacuo and the residue is taken up in water three times to hydrolyze the excess acetic anhydride.

The crude product obtained is then recrystallized from ethanol. A product is thus obtained which melts at 72-73 ° C, the analysis of which by R.M.N. and I.R. confirms that it is acetylamino-4 chloro-6 diethylamino-2 methylthio-5 pyrimidine.

Example 11.

Preparation of a mixture of 2,4-diamino-6 chloro-5-methylthio-pyrimidine (isomer A) and of diamino-4,6-chloro-2-methylthio-5 pyrimidine (isomer B).

1300 g of 2,4,4,6-methylthio-pyrimidine, 1,700 ml of isopropanol and 495 g of ammonia are introduced into a 5 liter autoclave. It is heated for 5 hours at 100 ° C. After cooling to room temperature, the precipitate formed is collected by filtration, washed with 700 ml of isopropanol and then with water, dried. 1010 g of a mixture of 2,4-diamino-6-chloro-5-methylthio-pyrimidine (isomer A) and 4,6-diamino-chloro-2-methylthio-5-pyrimidine (isomer B) are thus obtained, which corresponds to a yield of 93.6% relative to the starting 2,4,4,6-methylthio-pyrimidine trichloro.

This mixture melts at 160 ° C. Its analysis by thin layer chromatography on silica (elution with a chloroform / methanol mixture 90/10), by gas chromatography coupled with mass spectrometry, by infrared spectrometry and by nuclear magnetic resonance of carbon 13 shows that it contains approximately 89% of isomer A and 11% of isomer B.

Example 12.

Preparation of 2,4-diamino-6-chloro-5-methylthio pyrimidine (isomer A).

10 g of the mixture obtained in Example 11 are dissolved in 85 ml of concentrated hydrochloric acid. 55 ml of water are gradually added to the solution obtained. The precipitate formed is filtered, washed with water and dried. 2.9 g of a product are thus obtained, which essentially consists of the A isomer.

Example 13.

Preparation of a mixture of 2,4-diamino-6 chloro-5-methylthio pyrimidine (isomer A) + 4,6-diamino-2-chloro-5-methylthio pyrimidine (isomer B) enriched in isomer B

• Dans 500 ml d'eau contenant 1,2 g de PLURONIC L 92 (agent tensio-actif non ionique constitué par un copolymère d'oxyde d'éthylène et d'oxyde de propylène) on disperse par agitation 46 g de trichloro-2,4,6 méthylthio-5 pyrimidine finement broyée. Puis on introduit en 10 minutes 170 g d'une solution aqueuse d'ammoniac à 20%, en maintenant la température à 5°C. On laisse ensuite une nuit à la température ambiante, puis on filtre le précipité formé et le lave à l'eau. On recueille ainsi 42 g d'un produit qui est un mélange des deux composés isomères dichloro-4,6 amino-2 méthylthio-5 pyrimidine et dichloro-2,6 amino-4 méthylthio-5 pyrimidine, ainsi que le montre en particulier l'analyse par résonance magnétique nucléaire du carbone 13.

1st step:

• 46 g of 2-trichloro are dispersed in 500 ml of water containing 1.2 g of PLURONIC L 92 (non-ionic surfactant consisting of a copolymer of ethylene oxide and propylene oxide), 4.6 finely ground 5-methylthio pyrimidine. Then 170 g of a 20% aqueous ammonia solution are introduced over 10 minutes, while maintaining the temperature at 5 ° C. It is then left overnight at room temperature, then the precipitate formed is filtered and washed with water. 42 g of a product are thus collected, which is a mixture of the two isomeric compounds 4,6-dichloro-2 amino-5-methylthio-pyrimidine and 2,6-dichloro-4-amino-4-methylthio-5 pyrimidine, as shown in particular l carbon 13 nuclear magnetic resonance analysis.

• 40 g du mélange obtenu dans la 1 ère étape sont dissous dans 700 ml d'acide chlorhydrique concentré. A la solution obtenue on ajoute 200 ml d'eau. Il se forme un précipité a que l'on sépare par filtration. On ajoute au filtrat 120 ml d'eau. If se forme un nouveau précipité b que l'on sépare par filtration. On ajoute enfin au filtrat 260 ml d'eau puis 200 ml d'une solution
  
  d'hydroxyde de sodium. Il se forme un précipité c que l'on sépare par filtration.

2nd step:

• 40 g of the mixture obtained in the 1st stage are dissolved in 700 ml of concentrated hydrochloric acid. To the solution obtained is added 200 ml of water. A precipitate is formed which is separated by filtration. 120 ml of water are added to the filtrate. If a new precipitate b is formed which is separated by filtration. Finally, 260 ml of water and then 200 ml of a solution are added to the filtrate.
  
  sodium hydroxide. A precipitate c is formed which is separated by filtration.

The precipitate a (weight 6 g) consists essentially of the compound dichloro-4,6 amino-2 methylthio-5-pyrimidine. The precipitate c (weight 17.2 g) consists of the compound 2,6-dichloro-4 amino-5-methylthio pyrimidine.

• Dans un autoclave on introduit 16,5 g du précipité c obtenu à la 2ème étape, 150 ml d'isopropanol et 17 g d'ammoniac. On chauffe à 100°C pendant 3 heures et 15 minutes. Après refroidissement on filtre le précipité formé. On obtient ainsi 11,3 g d'un produit qui est un mélange des deux isomères A et B. La teneur en isomère B du mélange est de 20%.

3rd step:

• 16.5 g of precipitate c obtained in the 2nd step, 150 ml of isopropanol and 17 g of ammonia are introduced into an autoclave. The mixture is heated at 100 ° C for 3 hours and 15 minutes. After cooling, the precipitate formed is filtered. 11.3 g of a product are thus obtained, which is a mixture of the two isomers A and B. The content of isomer B in the mixture is 20%.

Example 14.

Preparation of pure diamino-2,4-chloro-5 methylthio-5 pyrimidine (isomer A) and pure diamino-4,6 chloro-2-methylthio-5 pyrimidine (isomer B).

The isomers A and B are separated by preparative liquid chromatography from the mixture obtained in the 3rd step of Example 13.

The mixture is dissolved in chloroform supplemented with 2.5% ethanol and the solution is introduced at the head of a column 25 cm long and 22 mm inside diameter, filled with silica gel with a particle size of 5 y known under the trade name LICHROSORB Si 60 (product marketed by the company Merck). Eluted with chloroform added with 2.5% ethanol. The fractions collected at the bottom of the column using a fraction collector are evaporated. 2.1 g of chloro-6 diamino-2,4 methylthio-5 pyrimidine, whose melting point is 171 ° C., and 0.9 g of chloro-2 diamino-4,6 methylthio-5 pyrimidine are thus obtained, whose melting point is 270 ° C.

Example 15.

In this example, the products according to the invention are formulated in the form of aqueous suspensions containing 5% of a surfactant called "TWEEN 20".

The quantities of suspensions applied are equivalent to 1000 I / ha, and the dilutions carried out are calculated so as to provide the following quantities of active material:

The suspensions are applied by spraying either on 10-day-old plants, which makes it possible to study the post-emergence action of the products, or on seeds deposited on the soil surface, which makes it possible to study the action of pre-emergence. These seeds are covered with 2 cm of soil just after application.

The plants and seeds are placed in 18 x 12 x 5 cm plastic containers filled with standard soil made up of 3 parts of sand, 1 part of potting soil and 1 part of clay. After treatment, the containers are placed on an automatic irrigation tablet in a greenhouse maintained at 22 ° C and at a humidity rate of 70%.

The plants tested are TRITICUM SP wheat, PHASEOLUS SP beans, BETA SP beet, SINAPIS SP mustard, TARAXACUM SP dandelion and ZEA SP corn.

The results are noted 14 days after the treatment for the post-emergence trials and 21 days after the treatment for the pre-emergence trials.

The results are collated in table I. In this table the herbicidal efficacy of the compounds according to the invention with respect to the plants tested is expressed by a figure which represents the percentage of destruction of the plants in the treated batches. This percentage is evaluated by taking as a reference the plants from untreated control lots. The number 0 therefore indicates that the condition of the plants is the same in the treated lots and in the control lots, the number 100 that the plants are completely destroyed in the treated lots, which corresponds to maximum efficiency.

Example 16.

The tests are carried out as in Example 15. Only the doses of active ingredient applied change. These doses are as follows:

The results are collated in Tables II and III. The figures appearing in these tables represent the vegetative energies of the plants of the treated batches, expressed as a percentage of the vegetative energy of the plants of the untreated controls. The number 100 therefore indicates that the vegetative energy of the plants in the treated lots is identical to that of the control plants, the number 0 that the plants are entirely destroyed in the treated lots.

Also shown in Tables II and III are the results for a reference herbicide (chlortoluron).

Example 17.

The tests are carried out as in Example 15, with the following doses of active material:

The plants tested are TRITICUM SP wheat, ORDEUM SP barley, AVENA SP oats, ORYZA SP rice, GOSSYPIUM SP cotton, SETARIA SP foxtail, PANICUM SP panic, PASPALUM SP crabgrass and soybeans . The compound according to the invention tested is that of Example 7.

The results obtained are collated in Table IV. The meaning of the figures in Table IV is the same as that of the figures in Table I. The number 0 indicates that the condition of the plants is the same in lots treated in the control lots, the number 100 that the plants are completely destroyed in the lots processed.

Example 18.

The product of Example 7 is applied in the open field, by spraying, on cultivated plants (wheat, zucchini, barley, broad beans, soybeans, sunflowers, rapeseed, corn, oats, peas, tomatoes) and unwanted advantices plants (chenopod , amaranth, nightshade, nightshade, milkweed, bindweed, seneçon, foxtail), either in pre-emergence of the plants immediately after sowing, or in post-emergence of the plants 15 days after sowing. The applied product doses are 2.5 or 5 kg / ha.

The results are noted 7, 14 and 100 days after the treatment (D + 7; 7 + 14; d + 100). These results are recorded in table V. The figures appearing in this table indicate, in the case of cultivated plants, the vegetative energy of the plants of the treated plots compared to that of the plants of the untreated control plots and, in the case of the plants weeds, the percentage of plants destroyed in the treated plots, this percentage being evaluated taking as reference the plants of untreated control plots.

For a cultivated plant, the note 100 therefore means that the vegetative energy of the plant is the same in the treated plots and in the control plots and the note O that the plant is entirely destroyed in the treated plots.

For an adventitious plant, the note O means that the state of the plant is the same in the treated plots and the control plots and the note 100 that the plant is entirely destroyed in the treated plots.

Example 19.

The product of Example 7 is applied by spraying on winter wheat cultures of the Lutin variety, at different stages of the culture (pre-emergence, 3 leaves, tillering, end of tillering). The applied product rates are 0.625 or 1.25 kg / ha.

20, 22, 35, 65 and 100 days after the treatment according to the cav (on this subject Table VI), the effect of the treatment is examined on the one hand on the cultivated plant (wheat), on the other hand on the plants unwanted weeds (speedwell, grazing ground, vulpin, chickweed, capsella).

In no case was phytotoxicity recorded against wheat. In Table VI are collected the results relating to the rate of destruction of weeds. The note 0 corresponds to a free plant, the note 100 to a completely destroyed plant.

Claims (13)

1. Compounds of the formula:

in which R₁ is an alkyl group having 1 to 5 carbon atoms, X₁ is a chlorine atom, X₂ is a

group in which R₂ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, R₃ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms and in addition, when R₂ is a hydrogen atom, may be a

group in which R is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, X₃ is a

group in which R₄ is a hydrogen atom and R₅ is a hydrogen atom or a

group, R being as defined above, and their salts with mineral or organic acids.

2. Compounds according to claim 1, characterised in that X₂ is a methylamino, ethylamino, isopropylamino, diethylamino or amino group, and X₃ is a NH₂ or

group.

3. The compound 2,4-diamino-6-chloro-5-methylthio pyrimidine.

4. The compound 4-amino-2-diethylamino-6-chloro-5-methylthio pyrimidine.

5. The compound 4-acetylamino-2-diethylamino-6-chloro-5-methylthio pyrimidine.

6. Process for the preparation of the compounds of formula (I) in which R₃ and R₅ are not

characterised in that a 2,4,6-trichloro-5-alkylthio pyrimidine of the formula:

in which X is a chlorine atom and R₁ is an alkyl group having 1 to 5 carbon atoms, is condensed with a compound of the formula

in which R₂ and R₃ have the same meanings as in claim 1 with the exception of the

meaning, and the 4,6-dichloro-5-alkylthio pyrimidine thus obtained is condensed with a compound of the formula

in which R₄ and R₅ have the same meanings as in claim 1, with the exception of the

meaning.

7. Process for the preparation of the compounds of formula (I) in which X₃ is a NH₂ group and X₂ is a

group in which R₂ and R₃ are identical R' alkyl groups, characterised in that a 2,4,6-trichloro-5-alkylthio pyrimidine of the formula:

in which X is a chlorine atom and R₁ is an alkyl group having 1 to 5 carbon atoms, is reacted with a tertiary amine of the formula N(R')₃, and the 4,6-dichloro-5-alkylthio pyrimidine thus obtained is condensed with ammonia.

8. Process for the preparation of the compounds of formula (I), in which X₂ and X₃ are NH₂ groups, characterised in that ammonia is condensed with a 2,4,6-trichloro-5-alkylthio pyrimidine of the formula:

in which X is a chlorine atom and R₁ is an alkyl group having 1 to 5 carbon atoms.

9. Use as herbicides of the compounds defined in each of claims 1 to 5.

10. Herbicidal compositions, characterised in that they contain, as active material, one or more compounds as defined in each of claims 1 to 5.

11. Herbicidal compositions, characterised in that they contain as active material, one or more compounds as defined in each of claims 1 to 5 and at least one other herbicide.

12. Herbicidal compositions according to each of claims 10 to 11, characterised in that the compound included as active material is 2-diethylamino-4-acetylamino-6-chloro-5-methylthio pyrimidine.

13. Herbicidal compositions according to each of claims 10 to 11, characterised in that the compound included as active material is 2,4-diamino-6-chloro-5-methylthio pyrimidine.