GB2179652A - Phthalide derivatives - Google Patents

Abstract

Phthalide derivatives having the general formula I <IMAGE> in which X is oxygen or sulphur; A represents an optionally substituted nitrogen-containing monocyclic heteroaromatic group, or an optionally substituted phenyl ring which is fused to at least one optionally substituted nitrogen-containing monocyclic heteroaromatic group; and R1 and R2, which may be the same or different, each independently represent a hydrogen or halogen atom, or an optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, alkaryl, hydroxyl, alkoxy, cycloalkoxy, alkenyloxy, alkynyloxy, alkoxycarbonylalkoxy, alkylthio, acyl, acyloxy, carboxyl, alkoxycarbonyl, or heterocyclic group or an amino group of formula -NR3R4, in which each of R3 and R4 individually is selected from a hydrogen atom, an optionally substituted alkyl, aryl and acyl group; or R1 and R2 together represent an oxygen or sulphur atom or an imino group of formula =NR3, in which R3 has the above meaning. The compounds are useful as herbicides.

Description

SPECIFICATION Phthalide derivatives The invention relates to certain phthalide derivatives, the preparation of such compounds, herbicidal compositions containing them and to their use in combating undesired plant growth.

It has been found that certain ether compounds of phthalide derivatives show a useful herbicidal activity.

These ether compounds should comprise a cyclic moiety with a nitrogen atom therein.

Accordingly, the present invention relates to phthalide derivatives having the general formula I

in which R, and R2, which may be the same or different, each independently represent a hydrogen or halogen atom, or an optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, alkaryl, hydroxyl, alkoxy, cycloalkoxy, alkenyloxy, alknyloxy, alkoxycarbonylalkoxy, alkylthio, acyl, acyloxy, carboxyl, alkoxycarbonyl, or heterocyclic group or an amino group of formula -NR3R4, in which each of R3 and R4 individually is selected from a hydrogen atom, an optionally substituted alkyl, aryl and acyl group; or R, and R2 together represent an oxygen or sulphur atom or an imino group of formula =NR3, in which R3 has the above meaning;X is oxygen or sulphur; and A represents an optionally substituted nitrogen-containing monocyclic heteroaromatic group, or an optionally substituted phenyl ring which is fused to at least one optionally substituted nitrogen-containing monocyclic heteroaromatic group.

The term "acyl" is used herein to denote the radical derived from an organic acid by the removal of a hydroxyl group; the organic acid may be a carboxylic acid (including carbamic acid derivatives) or a sulphonic acid, examples of suitable acyl groups being alkylcarbonyl, alkylcarbamoyl and alkylsulphonyl, e.g. acetyl, methylsulphonyl and dimethylcarbamoyl.

When the compounds of this invention contain an alkyl, alkenyl or alkynyl substituent group, this may be linear or branched and may contain up to 10, preferably up to 6, carbon atoms, suitable examples being methyl, ethyl, propyl, allyl and propynyl, and in the case of an alkyl group may also be substituted by a halogen, especially chlorine, atom, an alkoxy group such as a methoxy group, or an ester group such as alkoxycarbonyl, e.g. ethoxycarbonyl. When they contain a cycloalkyl substituent group this may contain from 3 to 10, preferably 5 to 8, carbon atoms, and is suitably cyclohexyl. When they contain a haloalkyl substituent group, this suitably contains up to 6, preferably up to 4, carbon atoms and the halogen atom is suitably fluorine or chlorine, trifluoromethyl being particularly preferred.When they contain an aryl substituent group, this is preferably a phenyl group which may optionally be substituted, for example by one or more halogen, especially chlorine, atoms. When they contain a heterocyclic group, this may, for example, be a pyrrole, pyrrolidine, pyridine, piperidine, furan or pyran ring. When any of the foregoing substituents are designated as being optionally substituted, the substituent groups which are optionally present may be any of those customarily employed in the development of pesticidal compounds, and/or the modification of such compounds to influence their structure/activity, persistence, penetration or other property. Specific examples of such substituents include halogen, especially chlorine, atoms and nitro, cyano, hydroxyl, alkoxy, e.g. methoxy, or ester, e.g. alkoxycarbonyl, groups.

Preferably X represents an oxygen atom, and R, and R2 are selected from a hydrogen atom, a C14 alkyl, C, 4 alkoxy or an aryl group. In particular compounds are preferred in which R, and R2 are both hydrogen or C14 alkyl groups.

It will be appreciated that when the nature of the substituents is such as to introduce an asymmetric carbon atom, then the resulting compound will exist in stereoisomeric forms. Also, some substituent combinations permit the existence of tautomeric forms. The scope of the present invention includes these different forms of the compounds and their mixtures, and herbicidal compositions containing the active ingredient in such isomeric forms and mixtures.

The heteroamatic group A in the phthalide derivatives according to the invention preferably contains one or two nitrogen atoms in the ring, and, when A is a phenyl ring fused to the heterocyclic ring, may also comprise other heteroatoms, such as sulphur or oxygen. Suitable examples of A are optionally substituted pyridyl, pyrazinyl, pyrimidinyl or pyradizinyl group, or an optionally substituted phenyl group fused with an optionally substituted pyrrole, pyrazole, imidazole, oxazole, thiazole, furazan or thiophenazan group. Preferred compounds are those in which A represents an optionally substituted pyridyl or benzofurazanyl group. When A is a pyridyl group, the position to which the pyridyl group is linked to the oxygen atom of the ether group is preferably the 2-position, although linkage on the 3- or 4-position is not excluded.

The group A is optionally substituted. Suitable substituents are selected from a halogen atom, especially a fluorine or chlorine atom, an alkyl group, in particular a Cur 4 alkyl group, a haloalkyl group, in particular trifluoromethyl group, a cyano and a nitro group.

The substituents may be present on any possible positions of the group A. Especially preferred are compounds in which A represents a pyridyl group of formula II

in which R5 is a halogen atom or a haloalkyl group and R6 is a halogen atom.

The invention further provides a process for the preparation of a phthalide derivative as defined above, which comprises reacting a phthaiide of formula Ill

with a compound of formula A-Z, wherein A, X, R1 and R2 have the meanings given above for formula I, and one of Q and Z represents a halogen atom or a nitro group, and the other represents a group of formula -OM, wherein M represents a hydrogen or alkali metal atom. Conveniently the reaction is carried out by reacting a compound of formula Ill wherein Q is hydroxyl with an alkali metal hydroxide or hydride, preferably in a suitable solvent, thereby forming an alkali metal salt, and the alkali metal salt is reacted with the compound A-Z, wherein Z represents a chlorine atom.The reaction of an alkali metal hydroxide with a compound of formula Ill is conveniently carried out in an alkanol solvent, e.g. ethanol. The latter reaction and also the reaction of the alkali metal hydroxide with the compound of formula Ill and also the reaction of the alkali metal salt with the chloro-compound is preferably carried out in a suitable aprotic organic solvent, e.g. dimethyl sulphoxide, sulpholane, dimethyl formamide, or dimethyl acetamide. The latter reaction is suitably carried out at elevated temperature, e.g. above 25"C and in particular between 40"C and reflux, conveniently under reflux, and also under an inert atmosphere such as nitrogen.

Compounds wherein X in formula I represents sulphur may be obtained from the corresponding oxygen analogues by reaction with phosphorus pentasulphide.

Compounds wherein X represents an oxygen atom, and in which group F1 is a hydrogen atom and R2 has one of the meanings defined above excluding hydrogen or hydroxyl, may be obtained from the corresponding compound wherein R2 represents hydroxyl by reaction with a reagent of formula HR2 wherein R2 is as defined for formula I excluding hydrogen or hydroxyl or, when R2 is a carboxylic acyloxy group, an acyl an hydride of formula Ac2O wherein Ac is an alkylcarbonyl group. The reaction is suitably carried out by refluxing the reaction mixture. In some cases the reactant HR2 can be used in excess to provide a convenient reaction solvent; in other cases it may be convenient to introduce the reagent HR2 as a solution in an organic solvent, e.g. acetonitrile or methyl ethyl ketone.

The compounds of general formula I have been found to show interesting activity as herbicides. Accordingly, the invention further provides a herbicidal composition comprising a compound of formula I as defined above in association with at least one carrier, and a method of making such a composition which comprises bringing a compound of formula I into association with at least one carrier.

The invention also provides the use of such a compound or composition according to the invention as a herhicide. Further, in accordance with the invention there is provided a method of combating undesired plant growth at a locus by treating the locus with a compound or composition according to the invention. Application to the locus may be pre-emergence or post-emergence. The dosage of active ingredient used may, for example, be from 0.05 to 4kg/ha. A carrier in a composition according to the invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated which may for example be a plant seed or soil, or to facilitate storage, transport or handling.A carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid, and any of the carriers normally used in formulating herbicidal compositions may be used. Preferably compositions according to the invention contain 0.5 to 95% by weight of active ingredient.

Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicates such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminium silicates, for example attapulgites and vermiculites; aluminium silicates, for example kaolinites, montmorillonites and micas; calcium carbonate, calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxides and synthetic calcium or aluminium silicates; elements, for example carbon and sulphur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes; and solid fertilisers, for example superphosphates.

Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons, for example benzene, toluene and xylene; petroleum fractions, for example kerosine and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene and trichloroethane.

Mixtures of different liquids are often suitable.

Agricultural compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surface-active agent facilitates this process of dilution.

Thus preferably at least one carrier in a composition according to the invention is a surface-active agent. For example the composition may contain at least two carriers, at least one of which is a surface-active agent.

A surface-active agent may be an emulsifying agent, a dispersing agent or a wetting agent; it may be non ironic or ionic. Examples of suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; fatty acid esters of glycerol, sorbitol, sucrose or pentaerythritol; condensates of these with ethylene oxide and/or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylocresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates of these condensation products; alkali or alkaline earth metal salts, preferably sodium salts, of sulphuric or sulphonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts of sulphonated castor oil, and sodium alkylaryl sulphonates such as dodecylbenzene sulphonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide.

The cnm';')3sitions of the invention may for example be formulated as wettable powders, dusts, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates and aerosols. Wettable powders usually contain 25, 50 or 75% w of active ingredient and usually contain in addition to solid inert carrier, 3-10% w of a dispersing agent and, where necessary, 0-10% w of stabiliser(s) and/or other additives such as penetrants or stickers. Dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant, and are diluted in the field with further solid carrier to give a composition usually containing 2-10% w of active ingredient.

Granules are usually prepared to have a size between 10 and 100 BS mesh (1.676 - 0.152 mm), and may be manufactured by agglomeration or impregnation techniques. Generally, granules will contain 2-75% w active ingredient and 0-10% w of additives such as stabilisers, surfactants, slow release modifiers and binding agents.

The so-called "dly flowable powders" consist of relatively small granules having a relatively high concentration of active Ingredient. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, co-solvent, 10-50% w/v active ingredient, 2-20% w/v emulsifiers and 0-20% w/v of other additives such as stabiRsers, penetrants and corrosion inhibitors.Suspension concentrates are usually compounded so as to obtain a stab3e, non-sedimenting flowable product and usually contain 10-75% w active ingredient, 0.5-15% w of dispersing agents, 0.1-10% w of suspending agents such as protective colloids and thixotropic agents, 0-10% w of other additives such as defoamers, corrosion inhibitors, stabilisers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be present dissolved in the formulation to assist in preventing sedimentation or as anti-freeze agents for water.

Aqueous dispersions and emulsions, for example compositions obtained by diluting a wettable powder or a concentrate according to the invention with water, also lie within the scope of the invention. The said emulsions may be of the water-in-oil or of the oil-in-water type, and may have a thick 'mayonnaise'-like consistency.

The composition of the invention may also contain other ingredients, for example other compounds possessing herbicidal, insecticidal or fungicidai properties.

The invention is illustrated in the following Examples.

EXAIlrSPE 1 Preparation of 5- (3,5- dichloro -2-pyridyloxy)phthallde

5-hydroxyphthalide (3.09) was dissolved in 50ml dry dimethyl sulphoxide (DMSO). Powdery potassium hydroxide (1 .4g) was added and the mixture was stirred for 11 hours at 60"C. 2,3,5-Trichloropyridine (3.65g) in 20ml DMSO was added and stirred for 22hrs at 60"C under nitrogen. Subsequently, the reaction mixture was poured onto ice, neutralised with diluted hydrochloric acid to pH7 and extracted with methylene chloride. The organic layer was dried over MgSO4.The solvent was removed and the residue was chromatographically purified over silica with methylene chloride as eluant, to yield a white solid, m.p. 129-1 30 C.

Analysis Calculated for C,3H7NO3CI2: C 52.7; H 2.4; N 4.7% Found : C 52.0; H 2.1; N 4.6% EXAMPLE 2 Preparation of 5- (5- trffluoromethyl-3- chloro -2 -pyridyloxy)phthallde

To 5-hydroxyphthalide (3.09) in 20ml of dry dimethyl formamide (DMF) was added a suspension of 11 g sodium hydride in DMF. The resulting mixture was stirred at ambient temperature for 2 hours. Subsequently, a solution of 2,3-dichloro-5-trifluoromethyl pyridine (4.359) in 10ml of DMF was added dropwise to the reaction mixture under nitrogen with stirring. Stirring was continued at 1 00 C for 3 hours. The reaction mixture was allowed to cool off and stand overnight, then it was poured into water, acidified with hydrochloric acid and neutralized with sodium bicarbonate to pH7.The mixture was extracted with methylene chloride. The organic layer was washed with water and dried. The solvent was then removed and the resulting oii was purified as in Example 1 to yield a white solid, m.p. 118-1 20 C.

Analysis Calculated for C,4H7NCIF303: C 51.0; H 2.1; N 4.25% Found C 51.0; H 2.1; N 4.3% EXAMPLE 3 Preparation of 5- (5-trifluoromethyl-2-pyridyloxyJphthalid

In a similar way as described in Example 2, sodium hydride (1.1 g) and 5-hydroxyphthalide (3.09) in DMF were ailowed to react with 3.659 of 2-chloro-5-trifluoromethylpyridine. After stirring for 20 hours at 1 00 C the reaction mixture was worked up as described in Example 2, to yield a pale yellow solid, m.p. 102-1 03 C.

Analysis Calculated for C,4H8NO3F3: C56.95; H 2.7; N 4.75% Found C 56.8; H 2.7; N 4.6% EXAMPLE 4 Preparation of 5- (6- chloro -3-pyridazinyloxy)phthalide

In a similar way as described in Example 1, 5-hydroxyphthalide (3.0g) and potassium hydroxide (1.4g) in 50ml DMSO were allowed to react with 3.0g of 3,6-dichloropyridazine. The reaction mixture was then poured into water, and extracted with methylene chloride. The organic layer was dried, the solvent was removed and the residue was chromatographically purified over silica and using chloroform as eluant. After recrystallization of the purified product in methanol, a solid was obtained, m.p. 150-1 53oC.

Analysis Calculated for C2H7N203Ci: C 54.9; H 2.7; N 10.7% Found C 54.6; H 2.6; N 11.1% EXAMPLES Preparation of 5- (7-chloro -benzofurazanyl-4- phthalide

Sodium hydride (0.5g), 5-hydroxyphthalide (3.0g) and 4,7-dichlorobenzofurazan (3.8g) were allowed to react in DMF, in the way as described in Example 2. After pouring the reaction mixture in water, the aqueous admixture was extracted with ether, the organic layer dried, the ether removed and the residue purified by chromatography over silica and using chloroform as eluant, yielding a yellow solid, m.p. 161-163"C.

Analysis Calculated for Cr4H7N204CI: C 55.5; H 2.3; N 9.3% Found C 54.9; H 2.5; N 9.3% COMPARATIVE EXAMPLE 6 Preparation of 5- (6-chloro-3, 1 -benzothiazole-2- oxy)phthalide

To illustrate that compounds containing a heteroaromatic group A which consists of a phenyl ring fused to a nitrogen-containing heteroaromatic group but which is linked to the oxygen atom of the ether group not by means of the phenyl group but by means of the fused heteroaromatic group, are inactive from a herbicidal point of view, the title compound was prepared and tested on herbicidal activity.

Similarly as described in Example 1, 5-hydroxyphthalide (1.5g), potassium hydroxide (0.7g) in DMSO were allowed to react with2,6-dichloro-3,1 -benzothiazole (2.05g). After pouring the reaction mixture in water and acidification of the aqueous admixture thus obtained, the admixture was extracted with ethyl acetate. The organic layer was dried and the ethyl acetate was removed to yield a residue which was purified chromatographically giving a solid m.p. 171-172"C.

Analysis Caiculate for Ca5H8NO3SCI: C 56.7; H 2,5; N 4.4% Found . C 56.5; H 2.6; N 4.3% EXAMPLE 7 Herbicidal Activity To evaluate their herbicidal activity, the compounds prepared were tested using as representative range of plants: maize, Zea mays (Mz); rice, Oryza sativa (R); barnyard grass, Echinochloa crusgalli (BG); oat, Avena sativa (0); linseed, Linum usitatissimum (L); mustard, Sinapsis alba (M); sugar beet, Beta vulgaris (SB) and soya bean, Glycinemax (S).

The tests fall into two categories, pre-emergence and post-emergence. The pre-emergence tests involved spraying a liquid formulation of the compound onto the soil in which the seeds of the plant species mentioned above had recently been sown. The post-emergence tests involved two types of test, viz., soil drench and foliar spray tests. In the soil drench tests the soil in which the seedling plants of the above species were growing was drenched with a liquid formulation containing a compound of the invention, and in the foliar spray tests the seedling plants were sprayed with such a formulation.

The soil used in the tests was a prepared horticultural loam.

The formulations used in the tests were prepared from solutions of the test compounds in acetone containing 0.4% by weight of an aikylphenol/ethylene oxide condensate available under the trade mark TRITON X-155.

These acetone solutions were diluetd with water and the resulting formulations applied at dosage levels corresponding to 5 kg or 1 kg of active material per hectare in a volume equivalent to 600 litres per hectare in the soil spray and foliar spray test, and at a dosage of level equivalent to 10 kilograms of active material per hectare in a volume equivalent to approximately 3,000 litres per hectare in the soil drench tests.

In the pre-emergence tests untreated sown soil and in the post-emergence tests untreated soil bearing seedling plants were used as controls.

The herbicidal effects of the test compounds were assessed visually twelve days after spraying the foliage and the soil, and thirteen days after drenching the soil and were recorded on a 0-9 scale. A rating 0 indicates growth as untreated control, a rating 9 indicates death. An increase of 1 unit on the linear scale approximates to a 10% increase in the level of effect.

The results of the tests are set out in the following Table, in which the compounds are identified by reference to the preceding examples.

TABLE I Compound of Soil drench 10/kg/ha Dosage Foliar spray Pre-emergence Ex. No. Mz R BG O L M SB S kg/ha Mz R BG O L M SB S Mz R BG O L M SB S 1 58442234 1 4465465600500000 2 54877587 5 6476758785967482 1 5254737731632260 3 32554365 5 5444646742343230 1 3233444411300120 4 00303404 1 0000000000000000 5 23640000 5 6465556600600210 1 4243334500200010 6 00000000 5 0000000000000000 1 0000000000000000 From the results presented in the table it appears that the 2-pyridyl ether phthalide derivatives show the greatest activity. Further it is apparent that the compound of Example 6, i.e. not according to the invention, shows little to no herbicidal activity.

Claims (10)

1. Phthalide derivatives having the general formula I

in which R1 and R2, which may be the same or different, each independently represent a hydrogen or halogen atom, or an optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, alkaryl, hydroxyl, alkoxy, cycloalkoxy, alkenyloxy, alkynyloxy, alkoxycarbonylalkoxy, alkylthio, acyl, acyloxy, carboxyl, alkoxycarbonyl, or heterocyclic group or an amino group of formula -NF3F4, in which each of R3 and R4 individually is selected from a hydrogen atom, an optionally substituted alkyl, aryl and acyl group; or R, and R2 together represent an oxygen or sulphur atom or an imino group of formula =no3, in which R3 has the above meaning;X is oxygen or sulphur; and A represents an optionally substituted nitrogen-containing monocyclic heteroaromatic group or an optionally substituted phenyl ring which is fused to at least one optionally substituted nitrogen-containing monocyclic heteroaromatic group.

2. Phthalide derivatives according to claim 1, in which F1 and R2 are selected from a hydrogen atom, a C14 alkyl, C, 4 alkoxy and an aryl group.

3. Phthalide derivatives according to claim 2, in which R, and R2 are both hydrogen or C14 alkyl groups.

4. Phthalide derivatives according to any one of claims 1-3, in which A represents an optionally substituted pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl group, or an optionally substituted phenyl group fused with an optionally substituted pyrrole, pyrazole, imidazole, oxazole, thiazole, furazan or thiophenazan ring.

5. Phthalide derivatives according to any one of claims 1X, in which A is an optionally substituted pyridyl or a benzofurazanyl group.

6. Phthalide derivatives according to claim 5, in which the pyridyl group is a 2-pyridyl group.

7. Phthalide derivatives according to any one of claims 16, in which A represents a group substituted by at least one substituent selected from a halogen atom, an alkyl, haloalkyl, cyano and nitro group.

8. Phthalide derivatives according to claim 7, in which A represents a pyridyl group of formula II

in which R5 is a halogen atom or a haloalkyl group and R6 is a halogen atom.

9. Phthalide derivatives according to claim 1 as described hereinbefore with particular reference to the Examples 1-5.

10. Process for the preparation of a phthalide derivative of formula I as defined in any one of claims 1-9, which comprises reacting a phthalide of formula III

with a compound of formula A-Z, wherein A, X, R, and R2 have the meanings as defined in any one of claim 1-9, and