GB2285045A - Herbicidal pyrazines and pyrimidines - Google Patents

Herbicidal pyrazines and pyrimidines Download PDF

Info

Publication number
GB2285045A
GB2285045A GB9425387A GB9425387A GB2285045A GB 2285045 A GB2285045 A GB 2285045A GB 9425387 A GB9425387 A GB 9425387A GB 9425387 A GB9425387 A GB 9425387A GB 2285045 A GB2285045 A GB 2285045A
Authority
GB
United Kingdom
Prior art keywords
compound
arom
group
general formula
optionally substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
GB9425387A
Other versions
GB9425387D0 (en
Inventor
Hans-Peter Niedermann
David Munro
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shell Internationale Research Maatschappij BV
Original Assignee
Shell Internationale Research Maatschappij BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shell Internationale Research Maatschappij BV filed Critical Shell Internationale Research Maatschappij BV
Publication of GB9425387D0 publication Critical patent/GB9425387D0/en
Publication of GB2285045A publication Critical patent/GB2285045A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/18—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Compounds of general formula <IMAGE> wherein one of X<1> and X<2> represents a nitrogen atom and the other represents a group -CR wherein R represents a hydrogen or halogen atom, a nitro, a cyano or hydroxyl group, or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkoxycarbonyl, alkylthio, amino or amido group; Q represents a hydrogen or halogen atom, a nitro, cyano or hydroxyl group, or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkoxycarbonyl, alkylthio, amino or amido group; n and m independently represent 0, 1, 2 or 3; and A and B independently represent an optionally substituted aryl or heteroaryl group, have herbicidal activity.

Description

HERBICIDAL COMPOUNDS This invention relates to novel substituted pyrimidine and pyrazine compounds, and to their use as herbicides. The invention also relates to a process for the preparation of such compounds.
In accordance with the present invention, there i*.
provided a compound of general formula
wherein one of Xl and X2 represents a nitrogen atom and the other represents a group -CR wherein R represents a hydrogen or halogen atom, a nitro, cyano or hydroxyl group, or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkoxycarbonyl, alkylthio, amino or amido group; Q represents a hydrogen or halogen atom, a nitro, cyano or hydroxyl group, or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkoxycarbonyl, alkylthio, amino or amido group; n and m independently represent 0, 1, 2 or 3; and A and B independently represent an optionally substituted aryl or heteroaryl group.
Included within the scope of the present invention are standard derivatives of such compounds of general formula I, such as salts and N-oxides.
Generally, when any of the above mentioned moieties comprises an alkyl, alkenyl or alkynl group, the group may be linear or branched and may suitably contain 1 to 10, preferably 1 to 6, and most preferably 1 to 4 carbon atoms. Suitable alkyl groups include methyl, ethyl and propyl. Suitable alkenyl groups include ethenyl and propenyl. Suitable alkynyl groups include ethynyl and propynl. When any groups are designated as being optionally substituted, the substituent groups which are optionally present may be any of those customarily employed in the development of herbicidal compounds, and/or the modification of such compounds to influence their structure/activity, persistence, penetration or other property.In relation to moieties defined above which include an optionally substituted alkyl, alkenyl or alkynyl group, specific examples of such substituents include halogen, especially fluorine, chlorine or bromine atoms, and nitro, cyano, hydroxyl, ClX alkoxy, C haloalkoxy, (C alkoxy)carbonyl, amino and C alkylamino groups. It is preferred, however, that alkyl, alkenyl and alkynyl moieties are unsubstituted, or halogensubstituted.In relation to moieties defined above which comprise an optionally substituted aryl or heteroaryl group, optional substituents include halogen, especially fluorine, chlorine and bromine atoms, and nitro, cyano, amino, hydroxyl, C1 alkyl, C4 haloalkyl (especially CF3) and C,4 alkoxy groups. 1 to 3 substituents may suitably be employed An optionally substituted amino or amido group may suitably be mono- or di-substituted by an alkyl group.
A halogen atom may most suitably be a fluorine, chlorine or bromine atom. A preferred aryl group is phenyl. A preferred heteroaryl group is pyrazole especially 3pyrazolyl.
Preferably, R represents a hydrogen atom or an optionally substituted alkyl, alkoxy, alkylthio or amino group.
Where R represents an optionally substituted alkyl, alkoxy or alkylthio group, the alkyl moiety of said group is preferably unsubstituted and preferably represents a methyl group.
Where R represents an optionally substituted amino group, said amino group is preferably substituted by alkyl groups which are preferably unsubstituted. A preferred optionally substituted amino group is a dimethylamino group.
More preferably, R represents a hydrogen atom.
Preferably, Q represents a hydrogen atom cr ar optionally substituted alkyl, alkoxy, alkylthio or amino group. More preferably, Q represents a hydrogen atom.
Preferably, when one of n and m represents 1, 2 or 3, the other represents 0.
Preferably, n and m independently represent 0 or 1.
Preferably, at least one of n and m represents 0.
A and B may independently represent an optionally substituted phenyl or a nitrogen-containing heteroaryl group. A preferred optionally substituted heteroaryl group includes one or two heteroatoms, each of which is preferably a nitrogen atom. A preferred optionally substituted heteroaryl group includes 5 or 6 ring atoms.
Preferably, A and B independently represent an optionally substituted phenyl, pyridyl, pyrazolyl or pyrimidinyl group.
A preferred optionally substituted pyridyl group is an optionally substituted 4-pyridyl group. A preferred optionally substituted pyrazolyl group is an optionally substituted 5-pyrazolyl group. A preferred optionally substituted pyrimidinyl group is an optionally substituted 4-pyrimidinyl group.
Preferably, A and B represent aryl or heteroaryl groups optionally substituted by a halogen atom or atoms or an optionally substituted alkyl group or groups.
Preferred halogen atoms include fluorine and chlorine atoms, with a fluorine atom being especially preferred.
A preferred optionally substituted alkyl group is an optionally substituted methyl group. Preferred optionally substituted methyl groups include an unsubstituted methyl group and a halogen substituted methyl group, especially a trifluoromethyl group.
Groups A and B are preferably unsubstituted or substituted by 1 or 2 atoms or groups. Preferably, A and B independently represent phenyl, 2-methylphenyl, 2fluorophenyl, 3-chlorophenyl, 3-fluorophenyl, 4chlorophenyl, 4-fluorophenyl, 3,5-dichlorophenyl, 3trifluoromethylphenyl, 3-trifluoromethyl-4-fluorophenyl, 2-chloro-pyrid-4-yl, l-methyl-3-trifluoromethylpyrazol-5 yl and 6-trifluoromethylpyrimid-4-yl.
The invention extends to a process for the preparation of a compound of general formula I as described above, the process comprising reacting a compound of general formula
where Xl, X2, Q, n and A are as described above and L is a leaving group, with a compound of general formula.
L2O----(CH2)m----B III wherein m and B are as described above and L2 is a leaving group.
Said compounds of general formulas II and III are preferably reacted together in the presence of an aprotic polar organic solvent. Tetrahydrofuran is a preferred solvent. The reaction mixture is preferably refluxed and, subsequently, the compound of general formula I may be isolated by standard techniques.
L' may represent a halogen atom or an alkylsulphonyl group. Where L1 represents a halogen atom, it preferably represents a chlorine or bromine atom, a chlorine atom being especially preferred. Where L1 represents an alkylsulphonyl group, it preferably represents a methylsulphonyl group.
Preferably, L represents a halogen atom when, in the target compound of general formula I, X' represents a nitrogen atom; or when X represents a nitrogen atom and the moieties A-(CH2) n~ and B-(CH2)m- are the same.
Preferably, L1 represents an alkylsulphonyl group when, in the target compound of general formula I, X represents a nitrogen atom and the moieties A-(CH2) n- and B-(CH2)",- are different.
Preferably, L2 represents a metal cation, for example an alkali metal ion, a sodium ion being especially preferred.
A convenient process for preparing compounds of general formula III involves reacting a compound of general formula HO ( CH2) m B IV with an alkali metal hydride, for example sodium hydride. The reaction is preferably carried out in the presence of a polar aprotic organic solvent, tetrahydrofuran being preferred.
Compounds of general formula II may be prepared using standard procedures. In a preferred embodiment, a compound of general formula II is prepared by reacting a compound of general formula
wherein Xl, X2 and Ll are as described above and L3 is a leaving group, with a compound of general formula A----(ch2)n----OL4 VI where A and n are as described above and L4 is a leaving group.
The conditions for the reaction of the compounds of general formula V and VI to prepare the compound of general formula II may be generally as described above for the preparation of compounds of general formula I from compounds of general formula II and III.
L3 may independently represent the same atoms or groups described above for Ll. In a preferred embodiment, L1 and L3 represent the same atoms or groups.
L4 may independently represent the same atoms or groups as described above for L2.
Where the moieties A-(CH2)- and B-(CH2)",- are the same in a compound of general formula I, the compound may be prepared by reacting one equivalent of a compound of general formula V, wherein L' and L7 suitably represent the same atom or group, with two equivalents of a compound of general formula III.
Where the moieties A-(CH,) - and B-(CH2)l,- are not the same in a compound of general formula I, the compound may be prepared by reacting one equivalent of a compound of general formula V with one equivalent of a compound of general formual VI and then the product of the reaction (ie a compound of general formula II) may be reacted with one equivalent of a compound of general fornula III to prepare the target compound.
Compounds of general formula II, III, IV, V and VI are generally known and/or may be prepared using conventional techniques.
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. Preferably there are at least two carriers, at least one of which is a surface-active agent.
The invention also provides a method of combating undesired plant growth at a locus, comprising application of such a compound or composition.
In a method as mentioned above, the dosage of the active ingredient, the compound of general formula I, may, for example, be from 0.01 to lOkg/ha, suitably 0.05 to 4kg/ha. The locus may be an agricultural or horticultural locus, comprising, for example, a plant or soil. In a preferred method the locus contains undesired plant growth and treatment is by foliar spray application.
The invention also provides the use of a compound of general formula I as a herbicide.
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, 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 pesticidal 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 silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminium silicates, for example attapulgites and vermiculites; aluminium silicates, for example kaolinites, montomorillonites 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, tor 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 nonionic or ionic. Examples of suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation products 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, sorbitan, sucrose or pentaerythritol; condensates of these with ethylene oxide and/or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example - octylphenol or p-octylcresol, 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 compositions 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, 3-10t w of a dispersina agent and, where necessary, 0-10t 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 '/2-10t 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 '/2-75t w active ingredient and 0-10t w of additives such as stabilisers, surfactants, slow release modifiers and binding agents.
The so-called "dry flowable powders" consist of relatively small granules having a relatively higher concentration of active ingredient. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, cosolvent, 10-50% w/v active ingredient, 2-20t w/v emulsifiers and 0-20% w/v of other additives such as stabilisers, penetrants and corrosion inhibitors.
Suspension concentrates are usually compounded so as to obtain a stable, 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, 0-10t 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 antifreeze 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 invention will now be described further, by way of example.
EXAMPLE 1 Preparation of 26-Dibenzoloxypyrazine [X'=N; X2=CH; Q=H; n=m=1; A=B=phenyl] Benzyl alcohol (2.16g; 20mmol) in tetrahydrofuran (15ml) was added over 15 minutes to a stirred suspension of sodium hydride (0.6g; 20mmcl; 80%) in tetrahydrofuran (20ml) at ambient temperature. After additional stirring for 30 minutes, a solution of 2,6-dichloropyrazine (1.49g; lOmmol) in tetrahydrofuran (10ml) was added to the mixture. The reaction mixture was then ref fluxed for 5 hours, cooled, diluted with toluene (50ml) and the inorganic matter separated by filtration.The filtered solution was then evaporated and purified by column chromatography to give a pale yellow oil (2.lg; 72%) which crystallized on standing to give colourless crystals (m.p.
48-5l0C) EXAMPLE 2 Preparation of 2-(3-trif1uoromethvlphenox)-6- benzoloxypyrazine [Xl=N; X2=CH; Q=H; n=l; m=O; A=Phenyl; 5=3- trifluoromethylphenyl] Benzyl alcohol (0.432g; 4mmol) in tetrahydrofuran (5ml) was added over 15 minutes to a stirred suspension of sodium hydride (0.12g; 4mmol; 80%) in tetrahydrofuran (5ml). After additional stirring for 30 minutes, a solution of 2,6-dichloropyrazine (0.596g; 4mmol) in tetrahydrofuran (5ml) was added to the mixture which was then stirred for a further 30 minutes. The solvent was removed by evaporation and sodium 3trifluoromethylphenolate (0.736g) and dimethylsulphoxide (4ml) were added. The mixture was then stirred for 72 hours at 80"C.After cooling to ambient temperature, the mixture was transferred to a silica gel column and purified using toluene/ethylacetate (20:1) as eluent, to give the title compound (1.32g; 95.4%) as a pale yellow oil.
EXAMPLE 3 Preparation of 2,4-Dibenzyloxypyrimidine [X=CH; X=N; Q=H; n=m=1; A=B=phenyl] Benzyl alcohol (2.16g; 20mmol) in tetrahydrofuran (lOml) was added dropwise over 15 minutes to a stirred suspension of sodium hydride (0.6g; 20mmol; 80%) in tetrahydrofuran (20ml) at ambient temperature. After stirring for 1 hour, a solution of 2,4-dichloropyrimidine (1.49g; lOmmol) in tetrahydrofuran (20ml) was added and the reaction mixture ref fluxed for 4 hours. After cooling to ambient temperature, the solvent was removed by evaporation and the residue purified on a silica gel column using toluene/ethylacetate (20:1) as eluent, to give the title compound (2.15g; 73.5%) as a clear colourless oil.
EXAMPLE 4 Preparation of 2-(2-chlorobenzyloxv)-4-(3- trifluoromethylphenoxy) pyrimidine [X=ch; X=N; Q=H; n-o; m-1; A=3-trifluoromethylphenyl; B=2-chlorophenyl] 2-Chlorobenzyl alcohol (0.67g; 4.71 mmol) in tetrahydrofuran (10ml) was added dropwise over 15 minutes to a stirred suspension of sodium hydride (0.16g; 5.4mmol; 80%) in tetrahydrofuran (2 Oml) at ambient temperature.
After stirring for a further 2 hours, a solution of 2methylsulphonyl-4- (3-trifluoromethylphenoxy) pyrimidine (1.5g; 4.71mmol) in tetrahydrofuran (lOml) was added and the mixture stirred for 72 hours at ambient temperature.
The solvent was removed by evaporation and the residue separated by column chromatography using toluene/ethylacetate (20:1) as eluent to give the title compound (1.28g; 71.3%) as a pale yellow oil.
EXAMPLES 5 TO 87 By processes analogous to the processes of Examples 1 to 4, the compounds of general formula I described in Table 1 were prepared. The Table notes the "Analogous Process" (Example No. 1, 2, 3 or 4) by means of which the Examples 5 to 87 were prepared.
Characterizing data for the compounds of Examples 1 to 87 is provided in Table 2.
TABLE 1
Compound Analogous X X2 Q n m A B of Process Example No.
1 1 N CH H 1 1 Phenyl phenyl 2 2 N CH H 1 0 Phenyl 3-trifluoromethylphenyl 3 3 CH N H 1 1 Phenyl phenyl 4 4 CH N H 0 1 3-trifluoromethylphenyl 2-chlorophenyl 5 1 N CH H 0 0 3-trifluoromethylphenyl 3-trifluoromethylphenyl 6 1 N CH H 0 0 2-chloropyrid-4-yl 2-chloropyrid-4-yl 7 1 N CH H 0 0 1-methyl-3- 3-trifluoromethylphenyl trifluoromethylpyrazol 5-yl 8 1 N CH H 0 0 1-methyl-3- 1-methyl-3 trifluoromethylpyrazol- trifluoromethylpyrazol 5-yl 5-yl 9 1 N CH H 0 0 2-chloropyrid-4-yl 3-trifluoromethylphenyl 10 1 N CH H 0 0 2-chloropyrid-4-yl 1-methyl-3 trifluoromethylpyrazol 5-yl 11 1 N CH H 0 0 3-trifluoromethyl-4- 3-trifluoromethyl-4 fluorophenyl fluorophenyl
Compound Analogous X X2 Q n m A B of Process Example No.
12 1 N CH H 0 0 1-methyl-3- 3-trifluoromethyl-4 trifluoromethylpyrazol- fluorophenyl 5-yl 13 1 N CH H 0 0 3-trifluoromethylphenyl 3-trifluoromethyl-4 fluorophenyl 14 1 N CH H 1 1 4-fluorophenyl 4-fluorophenyl 15 1 N CH H 1 1 2-methylphenyl 2-methylphenyl 16 1 N CH H 1 1 3-fluorophenyl 3-fluorophenyl 17 1 N CH H 1 1 3-chlorophenyl 3-chlorophenyl 18 2 N CH H 1 0 Phenyl 2-chloropyrid-4-yl 19 2 N CH H 1 0 Phenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 20 2 N CH H 1 0 Phenyl 3-trifluoromethyl-4 fluorophenyl 21 2 N CH H 1 0 2-methylphenyl 3-trifluoromethylphenyl 22 2 N CH H 1 0 2-methylphenyl 3-trifluoromethyl-4 fluorophenyl
Compound Analogous X X2 Q n m A B of Process Example No.
23 2 N CH H 1 0 2-methylphenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 24 2 N CH H 1 0 4-fluorophenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 25 2 N CH H 1 0 2-methylphenyl 2-chloropyrid-4-yl 26 2 N CH H 1 0 4-fluorophenyl 3-trifluoromethylphenyl 27 2 N CH H 1 0 4-fluorophenyl 3-trifluoromethyl-4 fluorophenyl 28 2 N CH H 1 0 4-fluorophenyl 2-chloropyrid-4-yl 29 2 N CH H 1 0 2-fluorophenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 30 2 N CH H 1 0 3-fluorophenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 31 2 N CH H 1 0 3-chlorophenyl 1-methyl-3 trifluoromethylpyrazol 5-yl
Compound Analogous X X2 Q n m A B of Process Example No.
32 2 N CH H 1 0 3-fluorophenyl 3-trifluoromethylphenyl 33 2 N CH H 1 0 3-fluorophenyl 3-trifluoromethylphenyl 34 2 N CH H 1 0 3-chlorophenyl 3-trifluoromethylphenyl 35 3 C-CH3 N H 0 0 3-trifluoromethylphenyl 3-trifluoromethylphenyl 36 3 CH N H 0 0 3-trifluoromethylphenyl 3-trifluoromethylphenyl 37 3 CH N H 0 0 4-chlorophenyl 4-chlorphenyl 38 3 C-CH3 N H 0 0 4-chlorophenyl 4-chlorphenyl 39 3 CH N H 0 0 3-trifluoromethylphenyl 3-trifluoromethylphenyl 40 3 CH N H 0 0 2-chlorpyrid-4-yl 2-chlorpyrid-4-yl 41 3 C-CH3 N H 0 0 2-chlorpyrid-4-yl 2-chlorpyrid-4-yl 42 3 CH N H 0 0 3-trifluoromethylphenyl 2-chlorpyrid-4-yl 43 3 CH N H 0 0 3-trifluoromethylphenyl 1-methyl-3 trifluoromethylphenyl 5-yl 44 3 CN(CH3)2 N H 0 0 3-trifluoromethylphenyl 3-trifluoromethylphenyl 45 3 CH(CH3)2 N H 0 0 3-trifluoromethylphenyl 2-chlorpyrid-4-yl
Compound Analogous X X2 Q n m A B of Process Example No.
46 3 CH N H 0 0 3-trifluoromethylphenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 47 3 COCH3 N H 0 0 1-methyl-3- 1-methyl-3 trifluoromethylpyrazol- trifluoromethylpyrazol 5-yl 5-yl 48 3 CSCH3 N H 0 0 3-trifluoromethylphenyl 3-trifluoromethylphenyl 49 3 CH N H 0 0 3-trifluoromethylphenyl 3-trifluoromethylphenyl 50 3 CH N H 0 0 1-methyl-3- 3-trifluoromethylphenyl trifluoromethylpyrazol 5-yl 51 3 CH N H 0 0 3-trifluoromethyl-4- 3-trifluoromethyl-4 fluorophenyl fluorophenyl 52 3 CH N H 0 0 1-methyl-3- 3-trifluoromethyl-4 trifluoromethylpyrazol- fluorophenyl 5-yl 53 3 CH N H 0 0 2-chloropyrid-4-yl 3-trifluoromethylphenyl 54 3 CH N H 0 0 2-chloropyrid-4-yl 3-trifluoromethyl-4 fluorophenyl
Compound Analogous X X2 Q n m A B of Process Example No.
55 3 CH N H 0 0 2-chloropyrid-4-yl 1-methyl-3 trifluoromethylpyrazol 5-yl 56 3 CH N H 0 0 6- 6 trifluoromethylpyrimid- trifluoromethylpyrimid 4-yl 4-yl 57 3 CH N H 0 0 3- 3-trifluoromethyl-4 trifluoromethylphenyl fluorophenyl 58 3 CH N H 0 0 3-trifluoromethylphenyl 3-chlorophenyl 59 3 CH N H 0 0 3-chlorophenyl 3-trifluoromethylphenyl 60 3 CH N H 0 0 3-chlorophenyl 3-chlorophenyl 61 3 CH N H 0 0 3-chlorophenyl 2-chloropyrid-4-yl 62 3 CH N H 0 0 3-chlorophenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 63 3 CH N H 0 0 3-chlorophenyl 3-trifluoromethyl-4 fluorophenyl 64 3 CH N H 1 1 4-fluorophenyl 4-fluorophenyl 65 3 CH N H 1 1 2-fluorophenyl 2-fluorophenyl
Compound Analogous X X2 Q n m A B of Process Example No.
66 3 CH N H 1 1 3-fluorophenyl 3-fluorophenyl 67 3 CH N H 1 1 2-methylphenyl 2-methylphenyl 68 3 CH N H 1 1 3-chlorophenyl 3-chlorophenyl 69 3 CH N H 1 1 3,5-dichlorophenyl 3,5-dichlorophenyl 70 4 CH N H 1 1 4-fluorophenyl 3-trifluoromethylphenyl 71 4 CH N H 1 1 4-fluorophenyl 1-methyl-3 trifluoromethylpyrazol 5-yl 72 4 CH N H 1 1 3-trifluoromethylphenyl phenyl 73 4 CH N H 1 1 1-methyl-3- phenyl trifluoromethylpyrazol 5-yl 74 4 CH N H 1 1 1-methyl-3- 2-fluorophenyl trifluoromethylpyrazol 5-yl 75 4 CH N H 1 1 1-methyl-3- 3-fluorophenyl trifluoromethylpyrazol 5-yl
Compound Analogous X X2 Q n m A B of Process Example No.
76 4 CH N H 0 1 1-methyl-3- 4-fluorophenyl trifluoromethylpyrazol 5-yl 77 4 CH N H 0 1 1-methyl-3- 2-methylphenyl trifluoromethylpyrazol 5-yl 78 4 CH N H 0 1 1-methyl-3- 3-chlorophenyl trifluoromethylpyrazol 5-yl 79 4 CH N H 0 1 2-chloropyrid-4-yl phenyl 80 4 CH N H 0 1 2-chloropyrid-4-yl 2-fluorophenyl 81 4 CH N H 0 1 2-chloropyrid-4-yl 3-fluorophenyl 82 4 CH N H 0 1 2-chloropyrid-4-yl 4-fluorophenyl 83 4 CH N H 0 1 2-chloropyrid-4-yl 2-methylphenyl 84 4 CH N H 0 1 2-chloropyrid-4-yl 3-chlorophenyl 85 4 CH N H 0 1 1-methyl-3- 3,5-dichlorophenyl trifluoromethylpyrazol 5-yl 86 4 CH N H 0 1 3-trifluoromethylphenyl 3-chlorophenyl
Compound Analogous X X2 Q n m A B of Process Example No.
87 4 CH N H 0 1 3-trifluoromethylphenyl 2-chlorophenyl TABLE 2
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 1 48-51 72.0 73.96 5.52 9.58 77.43 6.15 10.22 2 Oil 100 62.43 3.78 8.09 64.53 4.89 8.70 5.12 (s, 2H, CH2); 7.1 7.6 (m, 9H, arom) ; 7.97 (s, 1H, arom); 8.02 (s, 1H, arom); 3 Oil 73.5 73.95 5.52 9.58 73.19 5.38 9.60 5.4 (d, 4H, CH2); 6.4 (d, 1H, arom) ; 7.25-7.45 (m, 10H, arom) ; 8.2 (d, 1H arom); 4 Oil 71.3 56.78 3.18 7.36 57.98 3.42 7.42 5.3 (s, 2H, CH2); 6.6 (d, 1H, arom); 7.15-7.55 (m, 8H, arom); 8.4 (d, H, arom);; 5 87-89 74.0 54.0 2.5 7.0 54.0 2.5 7.0 6 96-97 26.9 50.17 2.41 16.72 52.40 3.56 17.62 7 105.5 70.0 47.54 2.49 13.86 49.21 3.08 15.01 8 103 79.6 41.19 2.47 20.58 42.94 2.88 21.85
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 9 101-102 61.7 52.26 2.47 11.43 54.51 2.93 11.94 10 68-70 43.5 45.24 2.44 18.84 48.47 2.94 19.28 11 Oil 35.3 49.56 1.85 6.42 50.45 2.03 6.16 7.0-7.3 (m, 6H, arom) ; 8.14 (s, 2H, arom) ; 12 88 73.4 45.51 2.15 13.27 47.53 2.50 14.10 13 Oil 44.9 51.69 2.17 6.70 52.59 2.86 6.33 6.9-7.5 (m, 7H, arom) ; 8.17 (s, 2H, arom) ;; 14 65 7.3 65.85 4.30 8.53 69.30 5.49 9.37 15 62-63.5 7.4 74.98 6.29 8.74 74.83 6.47 8.50 16 Oil 5.1 65.85 4.30 8.53 66.34 4.56 8.35 5.31 (s, 4H, CH2) ; 7.0 7.4 (m, 8H, arom) ; 7.88 (s, 2H, arom); 17 Oil 10.9 59.85 3.91 7.76 62.33 3.96 8.52 5.28 (s, 4H, CH2); 7.2 7.4 (m, 8H, arom) ; 7.88 (s, 2H, arom) ;
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 18 Oil 31.1 61.25 3.85 13.39 65.82 4.91 10.18 5.19 (s, 2H, CH2) ; 6.88 (d, 1H, arom) ; 7.09 (s, 1H, arom) ; 7.25-7.35 (m, 5H, arom) ; 8.02 (s, 1H, arom) ; 8.14 (s, 1H, arom) ; 8.31 (d, 1H, arom) ; 19 56-57 45.7 54.86 1.74 15.99 57.10 5.27 17.12 20 Oil 81.0 59.35 3.32 7.69 59.82 4.27 7.13 5.12 (s, 2H, CH2) ; 7.0 7.5 (m, 8H, arom) ; 7.95 (s, 1H, arom) ; 8.03 (s, 1H, arom) ; 21 Oil 77.7 63.33 4.20 7.77 56.45 5.48 7.90 2.27 (s, 3H, CH3) ; 5.13 (s, 2H, CH2) ; 7.1 7.6 (m, 8H, arom) ; 7.95 (s, 1H, arom) ; 8.01 (s, 1H, arom) ; 22 Oil 89.2 60.32 3.73 7.40 62.26 4.54 7.03 2.25 (s, 3H, CH3) ; 5.13 (s, 2H, CH2) ; 7.0 7.5 (m, 7H arom) ; 7.95 (s, 1H, arom) ; 8.02 (s, 1H, arom) ;
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 23 37-38 29.1 56.05 4.15 15.38 58.74 4.38 16.12 24 80 40.2 52.18 3.28 15.21 54.35 4.00 16.40 25 Oil 12.9 62.29 4.31 12.02 62.98 4.79 12.08 5.23 (s, 2H, CH2) ; 6.8 7.3 (m, 6H, arom) ; 8.03 (s, 1H, arom) ; 8.14 (s, 1H, arom) ; 8.32 (d, 1H, arom) ; 26 Oil 87.8 59.35 3.32 7.69 59.51 3.42 7.62 5.07 (s, 2H, CH2); 6.9 7.6 (m, 8H, arom) ; 7.97 (s, 1H, arom) ; 8.0 (s, 1H, arom) ; 27 Oil 94.8 56.55 2.90 7.33 58.70 3.28 7.66 5.08 (s, 2H, CH2) ; 6.9 7.5 (m, 7H, arom) ; 7.97 (s, 1H, arom) ; 8.02 (s, 1H, arom) ; 28 Oil 36.8 57.93 3.34 12.67 58.12 3.29 12.89 5.17 (s, 2H, CH2) ; 6.0 7.3 (m, 6H, arom) ; 8.02 (s, 1H, arom) ; 8.11 (s, 1H, arom) ; 8.35 (d, 1H, arom) ; 29 48 36.9 52.18 3.28 19.21 54.80 3.61 15.96
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 30 42 24.5 52.18 3.28 15.21 54.67 3.49 15.68 31 Oil 44.2 49.95 3.14 14.56 50.94 3.39 16.14 3.69 (s, 3H, CH3) ; 5.18 (s, 2H, CH2) ; 6.22 (s, 1H, arom) ; 7.0-7.3 (m, 4H, arom) ; 8.08 (s, 1H, arom) ; 8.15 (s, 1H, arom) ; 32 Oil 69.5 59.35 3.32 7.69 61.59 3.92 8.14 5.17 (s, 2H, CH2) ; 6.9 7.6 (m, 8H, arom) ; 7.95 (s, 1H, arom) ; 8.01 (s, 1H, arom) ; 33 Oil 99.2 59.35 3.32 7.69 59.78 3.77 7.57 5.08 (s, 2H, CH2) ; 6.8 7.6 (m, 8H, arom) ; 7.97 (s, 1H, arom) ; 8.04 (s, 1H, arom) ; 34 Oil 43.4 56.74 3.18 7.36 59.68 3.74 8.01 5.08 (s, 2H, CH2) ; 7.0 7.6 (m, 8H, arom) ; 7.97 (s, 1H, arom) ; 8.03 (s, 1H, arom) ; 35 98 74.0 55.08 2.92 6.76 55.23 3.09 6.45 36 84 89.0 54.01 2.52 7.00 53.88 2.45 7.75
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 37 120 53.5 57.6 3.0 8.4 57.6 3.2 8.3 38 82-83 46.9 58.8 3.5 8.1 60.5 4.1 8.0 39 84-85 37.5 54.01 2.52 7.00 54.25 2.67 6.81 40 100-102 44.8 50.17 2.41 16.72 51.12 3.39 16.98 41 90 71.0 51.60 2.89 16.05 52.61 3.16 16.56 42 50-51 61.8 52.26 2.47 11.43 53.59 2.74 11.81 43 91 54.5 47.54 2.49 13.86 49.64 2.89 14.59 44 54 81.2 54.18 3.41 9.48 55.47 3.52 9.05 45 53-55 68.2 52.63 3.43 13.64 53.41 3.62 13.70 46 104 48.3 48.33 3.38 15.66 49.70 3.74 15.94 47 65 63.7 41.19 2.47 20.58 42.79 3.01 21.16 48 53 60.9 53.03 2.81 6.51 53.81 2.95 5.94 49 67 14.0 51.12 2.71 6.28 52.05 2.65 6.76
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 50 Oil 66.0 47.53 2.49 13.86 47.19 3.12 13.69 3.75 (s, 3H, CH3) ; 6.1 (s, 1H, arom) ; 6.8 (d, 1H, arom) ; 7.25-7.55 (m, 4H, arom) ; 8.5 (d, 1H, arom) ; 51 62 6.9 49.56 1.85 6.42 49.32 3.06 6.75 52 Oil 61.0 45.51 2.15 13.27 44.23 2.84 13.00 4.75 (s, 3H, CH3) ; 6.05 (s, 1H, arom) ; 6.9 (d, arom) ;H, arom) ; 7.2 7.4 (m, 3H, arom) ; 8.5 (d, 1H, arom) ; 53 Oil 72.9 52.26 2.47 11.43 50.64 2.50 10.64 6.7 (d, 1H, arom) ; 7.0 7.5 (m, 6H, arom) ; 8.3 (m, 6H, arom) ; 8.45 (d, 1H, arom) ; 54 60-62 60.4 49.82 2.09 10.89 48.16 2.48 10.52 55 Oil 13.0 45.24 2.44 18.84 45.38 2.67 18.25 3.75 (s, 3H, CH3) ; 6.3 (s, 1H, arom) ; 6.85 (d, 1H, arom) ; 7.1-7.25 (m, 2H, arom) ; ; 8.4 (d, 1H, arom) ; 8.5 (d, 1H, arom) ;
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 56 175 33.2 41.60 1.50 20.79 41.31 1.32 20.83 57 Oil 83.2 51.69 2.17 6.70 52.44 3.02 6.01 6.7 (d, 1H, arom) ; 7.1 7.5 (m, 7H, arom) ; 8.4 (d, 1H, arom) ; 58 66-68 79.8 55.68 2.75 7.64 56.54 3.44 7.11 59 63 88.0 55.68 2.75 7.64 57.73 3.01 7.87 60 Oil 6.2 57.68 3.08 8.41 58.06 3.51 8.16 6.6 (d, 1H, arom) ; 7.0 7.3 (m, 8H, arom) ; 8.3 (d, 1H, arom) ; 61 84-88 39.2 53.92 2.71 12.58 55.39 3.59 12.99 62 67 64.5 48.60 2.72 15.11 50.32 3.32 15.95 63 Oil 80.9 53.07 2.36 7.28 53.71 2.86 7.33 6.65 (d, 1H, arom) ; 7.0-7.35 (m, 7H, arom) ; 8.35 (d, 1H, arom) ;; 64 54 1.5 65.85 4.30 8.53 68.40 5.01 8.71 65 62 50.0 65.85 4.30 8.53 64.82 4.45 8.79 66 62 68.2 65.85 4.30 8.53 66.07 4.50 8.61
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 67 Oil 70.0 75.45 5.70 8.80 73.47 6.32 8.59 2.35 (s, 3H, CH3) ; 2.45 (s, 3H, CH3); 5.35 (s, 2H, CH3) 5.4 (s, 2H, CH2) ; 6.4 (d, 1H, arom) ; 7.15-7.45 (m, 8H, arom) ; 8.2 (d, 1H, arom) ; 68 58-60 78.2 59.85 3.91 7.76 59.66 4.54 8.23 69 91-93 5.6 50.26 2.81 6.51 49.99 3.38 7.17 70 Oil 79.0 59.34 3.32 7.69 59.73 3.58 7.95 5.25 (s, 2H, CH3) ; 6.5 (d, 1H, arom) ; 7.0 7.6 (m, 8H arom) ; 8.2 (m, 9H, arom) ; 71 70-72 12.3 52.18 3.28 15.21 52.80 3.73 14.55 72 Oil 30.0 62.43 3.78 8.09 63.02 4.11 7.43 5.18 (s, 2H, CH3) ; 6.5 8.3 (m, 9H, arom) ; 73 79-80 57.0 54.86 3.74 15.99 55.66 4.09 16.15 74 56-58 53.7 52.18 3.28 15.21 53.50 3.71 14.16 75 45-46 53.7 52.18 3.28 15.21 52.69 3.36 14.72
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 76 57-59 56.0 52.18 3.28 15.21 52.23 3.34 14.61 77 80-82 57.2 56.04 4.15 15.38 56.40 4.49 14.99 78 65 46.3 49.95 3.14 14.56 49.97 3.27 14.03 79 Oil 58.5 61.25 3.86 13.39 60.49 3.60 12.70 5.3 (s, 2H, CH2); 6.6 (d, 1H, arom) ; 7.0 7.35 (m, 7H, arom) ; 8.35 (d, 1H, arom) ; 8.45 (d, 1H, arom) ; 80 Oil 44.9 57.93 3.34 12.67 56.54 3.32 12.07 5.35 (s, 2H, CH2) ; 6.65 (d,1H, arom) ; 7.0-7.4 (m, 6H, arom) ; 8.35 (d, arom) ;H, arom) ; 8.45 (d, 1H, arom) ; 81 Oil 57.2 57.93 3.34 12.67 57.31 3.32 12.53 5.3 (s, 2H, CH2) ; 6.65 (d, 1H, arom) ; 6.95-7.3 (m, 6H, arom) ; 8.35 (d, 1H, arom) ;; 8.45 (d, 1H, arom) ;
Compound Melting Yield Microanalysis H NMR data of oils in of Point C % CDCl3 Example Required Found No. %C %H %N %C %H %N 82 Oil 54.7 57.93 3.32 12.67 56.48 3.31 12.00 5.25 (s, 2H, CH2) ; 6.6 (d, 1H, arom) ; 7.0 7.35 (d, 6H, arom) ; 8.35 (d, 1H, arom) ; 8.45 (d, 1H, arom) ; 83 69 57.3 62.29 4.31 12.82 60.26 3.97 12.45 84 Oil 47.5 55.19 3.18 12.07 53.95 3.00 11.51 5.25 (s, 2H, CH2) ; 6.65 (d, 1H, arom) ; 7.0-7.3 (m, 6H, arom) ; 8.35 (d, 1H, arom) ; 8.45 (d, 1H, arom) ; 85 Oil 54.0 45.84 2.64 13.37 44.87 2.96 12.77 3.75 (s, 3H, CH3) ; 5.25 (s, 2H, CH2) ; ; 6.4 (s, 1H, arom) ; 6.6 (d, 1H, arom) ; 7.2 7.3 (m, 3H, arom) ; 8.45 (d, 1H, arom) ; 86 Oil 68.0 56.78 3.18 7.36 58.52 3.48 7.39 5.2 (s, 2H, CH2) ; 6.55 (d, 1H, arom) ; 7.1-7.65 (m, 8H, arom) ; 8.4 (d, 1H, arom) ; 87 72 65.2 56.78 3.18 7.36 57.93 3.44 7.44 Herbicidal Activity To evaluate their herbicidal activity, compounds of formula I according to the invention were tested using a representative range of plants: maize, Zea mavs (Z); rice, Orvza sativa (R); barnyard grass, Echinochloa crussalli (G); oat, Avena sativa (0); linseed, Linum usitatissimum (L); mustard, Sinapsis alba (M); sugar beet, Beta vulgaris (B) and soya bean, Glvcine max (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. 4t by weight of an alkylphenol/ethylene oxIde condensate available under the trade mark TRITON X-155. These acetone solutions were diluted with water and the resulting formulations applied at dosage levels corresponding to 5kg and lkg of active material per hectare in a volume equivalent to 900 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 Table 3 below.
A blank space in Table 3 indicates a rating 0. An asterisk denotes that a test was not undertaken, or was not completed. TABLE 3
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 1 5 1 2 5 3 6 5 6 1 5 4 2 7 3 5 8 7 7 1 3 5 3 3 7 7 5 3 5 3 4 2 4 8 7 4 3 2 1 2 2 2 5 7 2 4 4 4 2 2 6 5 5 5 2 8 5 5 9 8 5 2 7 2 7 8 1 4 1 7 4 4 8 7 4 5 6 7 5 2 1 1 2 1 5 5 2 5 4 4 6 6 5 2 5 3 2 4 3 1 4 1 3 2 4 6 5 4 2 2 1 6 7 3 5 3 4 6 2 4 5 2 5 7 8 8 4 2 2 2 4 3 1 1 5 6 8 8 4 2 4 1 7 6 5 7 7 5 7 7 6 5 5 8 6 8 8 9 7 5 4 5 6 8 8 1 5 4 7 8 8 4 2 4 2 8 7 8 6 7 8 7 6 7 9 5 5 7 5 8 7 8 8 9 8 5 2 8 6 7 9 8 6 1 6 2 8 6 8 8 9 7 2 7 5 6 9 8 2 9 4 3 6 5 4 5 6 5 2 7 2 6 8 8 4 2 5 1 5 2 1 6 5 8 8 2 2 2 10 8 7 6 7 8 9 9 7 5 6 8 5 8 9 9 8 6 6 9 7 4 8 9 4 1 2 7 4 7 9 9 7 5 5 8 6 2 5 9 2
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 11 5 6 2 5 6 5 9 9 6 5 5 1 2 2 4 5 8 7 4 4 4 12 5 4 6 5 6 6 7 2 5 6 2 8 8 8 9 9 8 7 2 9 8 7 9 9 5 1 5 8 8 8 9 9 7 5 8 6 5 8 8 2 13 5 5 2 5 2 4 8 9 7 1 4 2 2 2 4 7 8 5 14 5 1 15 5 1 16 5 4 3 1 2 17 5 2 7 2 2 8 5 2 4 4 5 2 1 2 7 2 2 2 18 * * * * * * * * 5 5 3 9 3 7 8 8 6 2 5 5 1 4 2 6 8 6 5 2 2 19 7 5 7 6 5 7 6 5 7 6 8 6 8 9 9 8 5 4 3 2 8 6 5 1 5 4 7 5 7 8 9 7 2 2 5 2 2 20 5 2 5 4 1 2 5 4 5 5 6 2 6 8 7 4 1 3 5 5 7 6 2 21 3 5 4 4 5 5 6 5 9 7 6 1 2 4 2 7 7 5
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 22 5 4 5 4 7 6 3 1 3 2 2 5 4 2 23 6 5 7 4 4 6 5 2 5 6 5 8 5 6 8 9 6 7 2 7 1 5 2 8 4 5 8 8 7 5 5 24 * * * * * * * * 5 6 4 8 6 8 9 9 8 4 2 8 4 5 9 9 2 1 5 2 7 5 7 9 9 8 2 7 2 2 6 5 25 6 7 4 1 4 5 2 5 5 4 7 5 7 9 9 6 2 5 2 6 2 1 2 2 6 2 4 8 7 5 4 5 26 4 6 5 6 5 1 5 6 4 8 5 5 9 9 7 5 4 2 6 5 1 5 2 6 4 3 8 8 6 2 2 5 4 27 5 2 5 4 5 5 7 4 5 9 9 6 5 4 1 6 2 1 2 5 2 2 8 8 5 2 2 2 28 6 5 8 5 4 7 9 2 5 5 4 8 5 8 9 9 7 5 7 8 5 1 2 3 7 2 7 8 8 6 4 5 4 6 29 6 5 8 7 4 8 7 2 5 6 3 8 7 8 9 9 8 4 2 9 5 5 9 7 2 1 4 7 7 7 9 9 7 2 7 2 4 7 5 30 7 6 8 6 4 8 8 2 5 4 4 8 5 8 9 9 9 2 4 3 3 8 8 2 1 4 3 3 2 6 9 9 8 4 3 31 2 4 3 2 3 4 2 5 2 3 6 5 6 9 9 6 3 3 1 3 4 3 5 8 8 5 2 2 32 * * * * * * * * 5 3 2 5 2 5 9 8 7 1 2 2 3 2 3 8 8 4
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 33 5 3 3 5 2 6 9 9 7 1 3 4 2 4 8 8 5 34 5 4 3 4 4 4 9 9 4 1 2 1 2 2 3 5 6 4 35 2 2 3 1 5 6 4 7 6 6 9 8 6 2 7 4 2 8 7 1 4 2 4 3 5 9 8 5 3 1 5 4 36 3 5 5 2 6 3 5 9 9 4 4 4 3 1 2 2 2 4 8 8 4 1 4 1 37 5 1 38 5 2 1 1 5 3 5 1 1 3 1 3 39 5 5 7 3 6 9 9 8 2 5 5 3 1 3 5 3 5 8 9 7 2 3 40 5 5 3 1 3 1 2 41 5 5 6 6 5 5 6 2 5 4 1 8 4 8 8 9 6 2 3 3 1 3 2 2 1 3 6 3 6 8 8 5 1 3 2 2 2 42 4 2 1 3 1 5 4 9 4 6 7 8 6 5 1 6 4 1 7 3 5 7 8 6 2 2 43 2 5 4 5 4 7 4 4 8 8 7 4 6 2 1 8 7 1 2 2 4 8 8 7 5 8 7
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 44 1 4 6 5 5 6 8 6 5 8 9 6 7 2 3 8 8 1 2 7 2 5 8 8 5 4 8 7 45 5 6 7 5 6 5 4 8 4 6 8 8 5 7 2 7 7 4 1 8 6 7 7 4 4 7 6 2 46 4 5 4 8 6 4 8 9 6 7 7 2 1 2 2 4 7 8 6 6 6 47 6 5 5 6 4 5 6 5 6 2 8 5 7 8 9 6 6 5 8 7 6 8 9 2 1 7 4 6 8 8 5 5 4 7 6 5 7 8 1 48 5 4 6 5 3 6 5 3 5 5 4 8 7 6 9 8 6 4 8 5 1 8 8 2 1 2 6 4 4 8 8 5 1 7 2 7 6 49 * * * * * * * * 5 2 4 1 4 8 9 6 1 2 2 7 8 4 50 5 6 3 4 5 5 6 8 7 8 9 9 8 2 9 5 5 9 9 5 1 5 7 5 4 8 9 7 2 6 4 4 8 8 4 51 5 7 6 6 1 * * * * * * * * * * * * * * * 52 4 6 3 7 5 5 6 8 7 8 8 9 8 5 2 9 8 8 9 9 5 1 5 8 5 7 8 9 7 4 1 8 6 6 9 9 5 53 4 6 2 1 4 6 2 5 4 6 4 5 9 8 6 3 5 6 1 3 5 2 2 8 8 5 2 2 54 5 2 6 4 1 4 5 2 5 4 7 3 6 9 9 6 5 7 8 2 1 3 6 2 5 8 8 5 2 5 4
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 55 6 4 6 5 7 6 4 2 5 4 5 3 6 8 9 6 4 5 4 2 4 1 1 2 2 5 7 8 5 2 2 2 56 5 1 57 * * * * * * * * 5 6 5 8 5 8 9 8 6 5 6 2 8 6 2 1 5 2 5 2 6 8 8 5 4 5 7 5 58 2 4 3 5 6 5 2 4 8 8 4 3 2 4 2 1 5 4 2 8 8 3 2 1 2 59 4 5 5 4 5 3 4 9 9 7 4 1 2 4 2 8 8 6 2 60 * * * * * * * * 5 5 2 3 8 8 6 3 1 4 2 8 7 6 3 61 5 2 2 5 7 6 3 4 1 2 2 7 5 2 62 5 4 6 3 5 8 8 5 2 3 2 1 5 2 4 8 8 4 2 2 63 5 3 5 2 4 8 9 5 4 5 6 1 2 2 8 8 5 2 2 5 64 * * * * * * * * 5 3 5 8 9 5 1 3 2 7 6 4 65 5 5 6 5 2 7 4 2 4 1 2 4 2 5 2 2
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 66 5 5 6 1 8 6 4 1 2 7 5 2 67 5 4 2 5 1 2 2 68 5 4 3 4 7 5 5 1 5 2 2 69 * * * * * * * * 5 1 70 5 3 1 8 7 4 9 9 6 4 2 7 4 1 7 3 2 9 9 5 3 71 5 2 6 2 3 4 6 5 3 1 8 6 6 9 9 4 7 3 3 8 8 1 3 8 4 6 9 9 4 4 3 7 8 72 4 2 5 6 2 5 2 1 5 6 4 8 7 6 8 8 8 4 2 8 6 2 8 8 6 1 5 8 6 6 8 8 7 2 1 8 4 1 8 8 0 73 7 7 8 7 5 8 9 4 5 7 6 8 7 8 9 9 9 3 5 9 5 5 9 9 7 1 4 5 8 7 8 9 9 9 2 2 9 4 4 9 9 5 74 7 6 8 6 4 7 8 3 5 4 3 8 7 8 9 9 9 2 2 9 6 4 9 9 3 1 3 2 8 6 8 9 9 8 2 6 3 2 8 8 3 75 7 6 7 6 3 8 9 2 5 7 5 9 6 8 9 9 9 4 3 9 7 7 9 9 6 1 5 4 8 5 8 9 9 9 4 3 9 5 5 9 9 5 76 7 6 6 6 2 6 9 2 5 7 2 8 8 8 9 9 9 4 2 9 6 4 9 9 4 1 5 1 8 6 8 9 9 8 3 2 8 4 3 9 9 4
Ex. Soil drech 10 kg/ha Dosage Foliar Spray Pre-emergence No. Z R G O L M B S kg/ha Z R G O L M B S Z R G O L M B S 77 6 4 7 6 2 5 4 2 5 4 2 8 4 7 9 9 8 3 7 2 2 7 8 1 4 2 8 4 7 9 9 8 2 2 28 4 2 4 5 4 7 4 6 8 9 6 5 2 8 8 2 1 3 5 2 5 7 8 2 2 7 7 79 8 6 8 5 6 8 9 5 5 4 2 8 4 8 9 9 7 5 2 9 6 6 9 9 4 1 4 7 2 8 8 9 6 4 7 4 5 8 9 2 80 6 5 7 4 5 6 5 3 5 5 7 3 7 9 9 6 3 5 2 9 7 2 1 2 5 2 5 8 8 5 2 6 5 81 7 6 8 4 5 7 8 6 5 6 8 5 8 9 9 8 6 3 9 4 5 8 9 6 1 5 7 4 7 9 9 7 4 2 7 2 8 8 82 6 5 7 5 4 8 8 5 5 5 8 5 8 9 9 8 5 8 4 3 9 8 4 1 2 7 4 7 8 9 6 4 6 2 1 8 8 2 83 5 4 8 4 4 7 6 2 5 5 8 4 8 9 9 6 2 6 5 8 1 2 6 4 6 8 9 5 4 2 5 84 4 5 1 1 5 2 1 5 4 5 3 7 8 9 6 5 6 5 2 1 3 2 2 4 8 8 4 2 5 2 85 5 4 5 4 4 8 8 6 1 2 2 2 1 7 7 5 86 4 6 4 4 3 2 5 5 2 8 5 5 9 9 5 2 4 7 8 1 4 7 4 4 8 8 4 3 7 5 87 4 1 4 6 2 0 5 5 3 8 5 5 9 9 7 2 3 7 5 1 2 2 7 4 4 8 8 6 2 5 4

Claims (12)

  1. CLAINS 1. A compound of general formula
    wherein one of Xl and x2 represents a nitrogen atom and the other represents a group -CR wherein R represents a hydrogen or halogen atom, a nitro, cyano or hydroxyl group, or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkoxycarbonyl, alkylthio, amino or amido group; Q represents a hydrogen or halogen atom, a nitro, cyano or hydroxyl group, or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkoxycarbonyl, alkylthio, amino or amido group; n and m independently represent 0, 1, 2 or 3; and A and B independently represent an optionally substituted aryl or heteroaryl group.
  2. 2. A compound according to Claim 1, wherein R represents a hydrogen atom or an optionally substituted alkyl, alkoxy, alkylthio or amino group.
  3. 3. A compound according to Claim I or Claim 2, wherein Q represents a hydrogen atom.
  4. 4. A compound according to any preceding Claim, wherein n and m independently represent 0 or 1.
  5. 5. A compound according to any preceding Claim, wherein at least one of n and m represents 0.
  6. 6. A compound according to any preceding Claim, wherein A and B independently represent an optionally substituted phenyl, pyridyl, pyrazolyl or pyrimidinyl group.
  7. 7. A process for the preparation of a compound of general formula I according to any preceding Claim, the process comprising reacting a compound of general formula
    where X', X2, Q, n and A are as described above and L is a leaving group, with a compound of general formula.
    L20 ~(CH2) ns B III wherein m and B are as described above and L2 is a leaving group.
  8. 8. A herbicidal composition comprising a compound of general formula I according to any of Claims 1 to 6 in association with at least one carrier.
  9. 9. A method of making a herbicidal composition according to Claim 8, the method comprising bringing a compound of general formula I according to any of Claims 1 to 6 into association with at least one carrier.
  10. 10. A method of combating undesired plant growth at a locus, comprising applying a compound of general formula I according to any of Claims 1 to 6 or a composition according to Claim 8 to the locus.
  11. 11. The use of a compound of general formula I according to any of claims 1 to 6 as a herbicide.
  12. 12. A compound of general formula I, a process for the preparation of such a compound, a herbicidal composition comprising such a compound, a method of making a herbicidal composition, a method of combating undesired plant growth and the use of a compound of general formula I, each being independently substantially as hereinbefore described with reference to the Examples.
GB9425387A 1993-12-27 1994-12-12 Herbicidal pyrazines and pyrimidines Withdrawn GB2285045A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP93120953 1993-12-27

Publications (2)

Publication Number Publication Date
GB9425387D0 GB9425387D0 (en) 1995-02-15
GB2285045A true GB2285045A (en) 1995-06-28

Family

ID=8213535

Family Applications (1)

Application Number Title Priority Date Filing Date
GB9425387A Withdrawn GB2285045A (en) 1993-12-27 1994-12-12 Herbicidal pyrazines and pyrimidines

Country Status (1)

Country Link
GB (1) GB2285045A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5723412A (en) * 1994-07-15 1998-03-03 Kureha Kagaku Kogyo Kabushiki Kaisha 2-benzyloxy-4-phenoxypyrimidine derivative, processes for producing the derivative and herbicidal composition containing the derivative
US5726128A (en) * 1994-09-14 1998-03-10 Kureha Kagaku Kogyo Kabushiki Kaisha Benzyloxypyrimidine derivative, processes for producing the same and herbicidal composition

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1010997A (en) * 1962-10-09 1965-11-24 British Petroleum Co Pyrimidine derivatives
GB1149212A (en) * 1965-07-24 1969-04-16 Bayer Ag Process for the production of substituted pyrimidines
GB1570555A (en) * 1977-04-05 1980-07-02 Taiho Pharmaceutical Co Ltd Anti-cancer composition

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1010997A (en) * 1962-10-09 1965-11-24 British Petroleum Co Pyrimidine derivatives
GB1149212A (en) * 1965-07-24 1969-04-16 Bayer Ag Process for the production of substituted pyrimidines
GB1570555A (en) * 1977-04-05 1980-07-02 Taiho Pharmaceutical Co Ltd Anti-cancer composition

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Agric. Biol. Chem. (1966), 30(9), 896-905 *
Chemical Abstracts 63:2817e *
Chemical Abstracts 64:15968h *
Chemical Abstracts 64:5090c *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5723412A (en) * 1994-07-15 1998-03-03 Kureha Kagaku Kogyo Kabushiki Kaisha 2-benzyloxy-4-phenoxypyrimidine derivative, processes for producing the derivative and herbicidal composition containing the derivative
US5726128A (en) * 1994-09-14 1998-03-10 Kureha Kagaku Kogyo Kabushiki Kaisha Benzyloxypyrimidine derivative, processes for producing the same and herbicidal composition

Also Published As

Publication number Publication date
GB9425387D0 (en) 1995-02-15

Similar Documents

Publication Publication Date Title
EP0488474B1 (en) Herbicidal carboxamide derivatives
US4543413A (en) Sulphonyl derivatives of N-phenyl pyridineamines
EP0013581B1 (en) Tetrahydrofuran derivatives, a process for their preparation, herbicidal compositions containing them and a method of controlling undesired plant growth using them
US5759956A (en) Herbicidal compounds
US5262388A (en) Herbicidal compounds
EP0015628A1 (en) Use as fungicides of pyridyliminomethylbenzene derivatives and acid-addition salts thereof; pyridyliminomethylbenzene derivatives and their acid-addition salts; a process for preparing such compounds and intermediates for use in such process; and fungicidal compositions comprising such compounds
US5371061A (en) Herbicidal picolinamide derivatives
EP0434132A2 (en) Herbicidal acrylonitrile derivatives
EP0700394B1 (en) Herbicidal thiazole derivatives
GB2277930A (en) Herbicidal picolinamide derivatives
GB2285045A (en) Herbicidal pyrazines and pyrimidines
AU657022B2 (en) Sulphonamide herbicides
GB2223946A (en) Herbicidal compositions and their use
EP0286735B1 (en) Diphenyl ether derivatives
EP0149269B1 (en) Heterocyclic herbicides
EP0280367B1 (en) Glycine compounds
GB2201672A (en) Diphenyl ether compounds
US4000149A (en) Herbicidal amide derivatives
US5508251A (en) Herbicidal methods and compositions comprising epoxy compounds
NZ225977A (en) Phenoxy phthalide derivatives and herbicidal compositions
EP0123327B1 (en) Chloroacetanilides, their preparation, their use, compositions containing them, and method of combating undesired plant growth
US3959299A (en) Herbicidal amide derivatives
GB2203739A (en) Herbicidal tetrazoles
GB2212156A (en) Diphenyl ether derivatives as herbicides
GB2179652A (en) Phthalide derivatives

Legal Events

Date Code Title Description
WAP Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1)