IL27664A - 2-amino-6-acyloxy(sulfonyloxy)-pyrimidines and biocidal compositions containing them - Google Patents

Description

- AM O - 6 - AC YLOXYCi§U LFON YLOXY) - P YRIMID1 ES AND BlOCiDAL COMPOSITIONS CONTAINING THEM 27664/3 This invention relates to new pyrimidine derivatives* to processes for making them, to biologically active compositions containing them and to methods for combating pests.

Pyrimidine compounds have been described which correspond to the formula: - wherein X is a group NR 3 and ΕΛ is hydrogen or alkyl; A is a hydro v carbon linking gpoup; and R and R are hydrogen or alkyl or together 1 £ with the adjacent nitrogen atom represent a heterocyclic ring* There is no disclosure however, in this document (British Patent Specification No* 767922)* or in any other document in the literature, to the effect that the 2-amino-pyrimidines of the present invention possess valuable anti-fungal properties, especially systemic fungicidal activity! that is to say when watered as an aqueous solution around the roots of a plant! they are capable of being taken up into the plant to combat fungal disease affecting it.

In the reference Nogaka Seisan Gijetsu 9, 17-22, 1963 (C. A. 61, 6S00h-6301b, 1964) there is a disclosure of the possession of in vitro anti-fungal activity in certain specific 2, 4, 6 -substituted pyrimidines. There is no disclosure in this reference of the valuable systemic anti-fungal properties possessed by the Compounds of the present invention. Indeed the combinations of substituent groups recited in the reference point away from those of the present invention in that they indicate that the substituents should be the same at all positions and feither chlorine, hydroxy or amino. Further more, the 2-ethyiamino substituent is stated to produce a lower activity than the 2- chloro- compound and the reference in this respect again points away from the present invention.

The invention provides a pyrimidine derivative having the formula: - or a salt thereof, wherein IL^ and fig represent hydrogen atoms* lower alkyl radicals* a halophenyl radical, a piperidino radical* a morpholino radical, or a 1-meth 1 i erazin- -yl radical; fij represents a hydrogen atom, a lower alkyl radical or a phenyl radical; fi^ represents an atom of hydrogen or bromine, a lower alkyl, lower alkenyl, or benzyl radical* or a nitro group; X represents anatom of oaygen or sulphur; and is a carbonyl or sulphonyl group bearing directly, or through an atom of oaygen or sulphur* a lower alkyl radical, a lower alkenyl radical, a phenyl radical or a nitro-, halo-, lower alkyl- substituted phenyl radical* a piperidino radical* a furyl radical or a styryl radical.

Preferred pyrimidine derivatives according to this invention are those having the general formula set out above wherein and fi^ represent hydrogen* or lower alkyl radicals) fi^ represents hydrogen* a lower alkyl radical or a phenyl radical; fi^ represents an atom of bromine* a lower alkyl* lower alkenyl or benzyl radical* and is a carbonyl or sulphonyl group bearing a lower alkyl radical* a lower alkoxy radical, a lower alkylthio radical* a phenyl radical or a nitro-, lower alkyl- or halo-substituted phenyl radical, a phenylthio radical, an alkenyl radical* an aralkenyl radical or a piperidino or furyl radical; or a salt thereof.

Particular biologically active pyrimidine derivatives according to the invention are those wherein and are hydrogen or lower alkyl radicals; is a lower alkyl radical; is a lower alkyl radical having 2 to 6 carbon atoms; and is a carbonyl or sulphonyl group bearing a lower alkyl radical, a lower alkoxy radical, a phenyl radical or a styryl radical* Preferred particularly biologically active pyrimidine derivatives are those wherein fi^ and fi^ are both methyl radicals or IL^ is hydrogenand Eg is an ethyl radical; it. is a methyl radical; is a butyl or amyl radical; X is an atom of oxygen; and fi^ is lower alkyl, lower alkoxy or phenyl radical* Specific pyrimidine derivatives of the invention which have been found to be particularly useful are listed in the Table I below. The headings to the columns of the Table correspond to the substituent groups on the pyrimidine ring in the general formula set out above* TABLE I TABLE I continued TABLE I continued TABLE I continued Compound No.14 in Table I above is readily hydrolyeed by water. in this specifiQation the numbering of the pyrimidine ring is as follows It may be noted that the 4- a d 6- positions are equivalent.

As suitable salts of the pyrimidine derivatives of this According to a further feature of the invention, we provide the novel pyrimidine derivatives listed in Table ί herein above.

The invention also provides a process for making the pyrimidine derivatives of this invention which comprises reacting a compound of the formula: * wherein R^ , Rg, ftg, R^ and X have any of the meanings stated above with an acyfOr sulphonyl halide of the formula: - R 5- - . Hal wherein Rg has any of the meanings stated above and Hal represents a halogen atom under conditions where the hydrogen halide which is formed is removed as it is produced.

The f oregoin¾iprocess is preferably carried out in the presence of a dilv.ent as a reaction medium and suitable diluents include substances acting as solvents for either or both of the reastants. Suitable solvents are organic solvents, for example benzene, toluene, lower aliphatic ketones such as methyl ethyl ketone or acetonitrile. A particularly preferred solvent is ethyl acetate.

The hydrogen halide produced during the reaction may be removed, for example, by carrying out the reaction in the presence of an acid acceptor. Suitable acid acceptors are bases or a salt of a strong base and a weak acid. If a base is used it may be, for example, a tertiary amine. Preferred tertiary amines are triethylamine and pyridine. The base may also be, for example, an alkali or alkaline earth metal hydroxide, for example, sodium hydroxide. If a salt of a strong base and a weak acid is used as the acid acceptor then a suitable salt is an alkali or alkaline earth metal carbonate. A preferred such salt is potassium carbonate.

The invention further provides a process for making the pyrimidine derivatives of the invention which comprises reacting the appropriate acyl or sulphonyl halide with a metallic salt of the appropriate 6-hydroxy- or 6-mercapto- pyrimidine, if necessary in the presence of a solvent to facilitate the reaction.

Suitable solvents include those recited above.

The pyrimidine derivatives of the invention possess activity against a wide variety of fungal diseases including the following specific diseasesj- Puecinia recondita (rust) on wheat Phytophthora infestans (late blight) on tomatoes Sphaerotheca fuliginea (powdery mildew) on cucumber Erysiphe graminis (powdery mildew) on wheat and barley Podosphaera leucotricha (powdery mildew) on apple Uncinula necator (powdery mildew) on vine Plasmopara viticola (downy mildew) on vine Piricularia oryzae (blast) on rice Venturia inaequalia (scab) on apple Pythium ultimum (seedling rot) on peas The compounds of the present invention are toxic towards a variety of insect pests including mosquito larvae (Aedes aegyti), black aphids (Aphis abae). green aphids (Macrosiphum pisi), red spider mites (Tetranyehus telarius), mustard beetles (Riaedon coehleariae). and root knot nematodes (Meloidogyne incognita).

A particularly useful feature of the activity of the pyrimidine derivatives of the invention is their systemic effect, that is to say, their ability to move throughout the plant to reach any part thereof bearing a fungal infection and/or insect infestation and to combat the same.

We have found that the biological activity of the novel pyrimidine derivatives of the invention is decreased if both and are hydrogen, or if is an alkyl radical containing more than 7 carbon atoms* A particularly useful pyrimidine derivative is that in which and are both methyl, fi^ is methyl, is is 0-CO-GgHj., that is Compound No.10 in the foregoing Table I.

According to a preferred embodiment of the invention, we accordingly provide fungicidal compositions comprising as active ingredient 2-dimethylamino-4-methyl-5-n-butyl^-^henylcarbonyloxy-pyrimidine.

Other particularly use ul pyrimidine derivatives are the compounds numbered 8, 10, 12, 13, 27» 28, 39, 40 and 41 in Table I above.

The biologically active pyrimidine derivatives of this invention are used to combat plant pests in a number of ways. Thus they can be applied to the foliage o n In a further aspect, therefore, the invention includes a method for the combating of undesired fungal infections in plants which comprises applying to the locus of the plant a pjrimidine derivative as hereinbefore defined or a composition as hereinafter defined* In a yet further aspect the invention includes a method of combating insect infestations in plants whic comprises applying to the locus of the plant an iasecticidically active pyrimidine derivative as hereinbefore defined or a composition as hereinafter defined.

In yet a further aspect the invention includes a method for treating agricultural soil comprising applying to the soil a pyrimidine derivative as hereinbefore defined or a composition as hereinafter definedo The invention includes, therefore, a method of combating plant pathogens which comprises applying to a plant, or to seed thereof, a pyrimidine derivative as hereinbefore defined or a composition as hereinafter defined„ The pyrimidine derivatives of this invention are preferably used in the form of com ositions and these compositions may be used for agricultural and horticultural purposes,, The type of composition used in any instance will depend upon the particular purpose for which it is to be used« The compositions may be in the form of dusting powders or granules wherein the active ingredient is mixed with a solid diluent or carrier° Suitable solid diluents or carriers may be, for example, kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller's earth, gypsum, Hewitt °s earth, diatomaceous earth and China clay. Compositions for dressing seed, for example, may comprise an agent assisting the adhesion of the composition The compositions may also be in the form of dispersible powders or grains comprising, in addition to the active ingredient, a wetting agent to facilitate the dispersion of the powder or grains in liquids* Such powders or grains may include fillers, suspending agents and the like.

The compositions may also he in the form of liquid preparations to be used as dips or sprays which are generally aqueous dispersions or emulsions containing the active ingredient in the presence of one or more wetting agents, dispersing agents, emulsifying agents or suspending agents.

Wetting agents, dispersing agents and emulsifying agents may be of the cationic, anionic or non-ionic type. Suitable agents of the cationic type include, for example, quaternary ammonium compounds, for example, cetyltrimethyl-ammonium bromide. Suitable agents of the anionic ty e include, for example, soaps, salts of aliphatic monoesters of sulphuric acid, for example sodium lauryl sulphate, salts of sulphonated aromatic compounds, for example sodium dodecyl-benzenesulphonate, sodium, calcium or ammonium lignosulphonate butyl-naphthalene sulphonate, and a mixture of the sodium salts of diisopropyl- and triisopropyl- naphthalene sulphonio acids. Suitable agents of the non-ionic type include, for example, the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol or cetyl alcohol, or with alkyl phenols such as octylphenol, nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acide and hexitol anhydrides, the condensation products of the said partial esters with Suitable suspending agents are, for example, hydrophilic colloids, for example polyvinylpyrrolidone and sodium carboxymethylcellulose, and the vegetable gums, for example gum acacia and gum tragacanth.

Theaqueous dispersions or emulsions may be prepared by dissolving the active ingredient or ingredients in an organic solvent which may contain one or more wetting, dispersing or emulsifying agents and then adding the mixture so obtained to water which may likewise contain one or more wetting, dispersing or emulsifying agents. Suitable organic solvents are ethylene dichloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, methylnaptthalene, xylenes and trichloroethylene.

The compositions to be used as sprays may also be in the form of aerosols wherein the formulation is held in a container under pressure in the presence of a propellent such as fluorotrichloromethane or dichloro-difluoromethane.

By the inclusion of suitable additives, for example for improving the distribution, adhesive ower and resistance to rain on treated surfaces, the different compositions can be better adapted for the various uses for which they are intended,, The pyrimidine derivatives may also be conveniently formulated by admixing them with fertilizers. A preferred composition of this type comprises granules of fertiliser material incorporating, for example coated with, a pyrimidine derivative.. The fertiliser material may, for example, comprise nitrogen or phosphate-containing substances.

In yet a further aspect of the invention, therefore, we provide a fertiliser composition comprising a pyrisddine derivative as hereinbefore definedo The compositions which are to be used in the form of aqueous dispersions ©r emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient or ingredients, the said concentrate to be diluted with water before use<> These concentrates are often required to withstand storage for prolonged periods and after such storage, to be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipments The concentrates may conveniently contain from 10-8¾S by weight of the active ingredient or ingredients and generally from 25-60 by weight of the active ingredient or ingredients. When diluted to form aqueous preparations, such preparations may contain varying amounts of the active ingredient or ingredients depending upon the purpose for which they are to be used, but an aqueous preparation containing between 0°00¾g and 1°G$ by weight of active ingredient or ingredients may be usedo It is to be understood that the biologically active compositions of this invention may comprise, in addition to a pyrimidine derivatives one or more other compounds having biological activity. They may also incorporate one or more stabilizing agents, for example epoxides, for example epichlorhydrino The invention is illustrated by the following Examples, those numbered 1 t© 5 exemplifying methods of containing various of the pyrimidine derivatives as active ingredient. In the latter group all references to percentage amounts of constituents are by weight and are based on the weight of the compositions as a whole* EXAMPLE I 2-Dimethvlamino-i~methyl'-6--( '>"nitrophen7l)carbonyl-oxy-5-n-propylpyriiaidine, (Compound No, 1, Table i) having the formulas- was prepared as follows: 2- methylamino-4-methyl-6-hydrQxy-5-n-propylpyrinddine (1*95 g»> 0*01 mole) was added to a solution of sodium (0*23 g., 0*01 mole) in dry ethanol (25 ml.). The solution was kept at 1*0°C for 1 hour, the solvent removed in vacuo, and the residue dried by azeotropic distillation with benzene. To the residue was added dry benzene (25 ml.) and freshly prepared p-nitrobenzoyl chloride (2*3 g»» 0*012 mole) and the reaction mixture stirred and refluxed for 4 hours. The cooled mixture was shaken with ice-cold 5$ aqueous sodium hydroxide solution, washed with water until the washings were neutral, and the benzene layer dried (N^SO^).

Removal of the benzene, ollowed by removal of last traces of solvent at the oil pump, gave a viscous residue which crystallised on trituration with petroleum ether.

Recrystallisation from ethanol gave a product, m.p.109 C. (1·8 g„ 55H).

Although the Above reaction was conducted in benzene, other solvents such as toluene, lower aliphatic ketones such as methyl ethyl ketone, acetonitrile and ethyl acetate were found to be suitable for the purpose. The preferred solvent is ethyl acetate.

The following compounds were alsoprepared by the method of Example 1.

EXAMPLE 2 S-(5-B-Butyl-2-diiaethylamino-4-methyl-6-pyrimidyl) O-ethylthiolcarbonate (Compound No.18, Table I) having the formula:- was prepared as follows$- methyl-6-mercapto-pyriiaidine (6*75 g«) was dissolved in a solution of sodium hydroxide (1*3 g„) in water (100 ml«) · Ethyl chloroformate (3«3 g.) was added and the reaction mixture stirred at room temperature for 3 hours. The product was obtained by extraction with ether. The ether extracts were washed with water, dried (Na^SO^), and the solvent removed to leave a viscous ©il9 n^ 26 « 1«5W* » !Ehe following compound was also prepared by the method of Example 2* Compound No* Physical Characteristics 33 17 -177°/0"12 mm , 1°6008 EXAMPLE 3 This Example illustrates the preparation ef " -butyl-2-dime hylaiidno- ~®t ©xy"carbo yl©^-6"methyl° pyrimidin© (Compound N©« 38, Table l) having the structure; To a solution of 5~n~butyl~2~dimethylamino~4~hydroxy- =» methyl pyrimidin© (5°0 go) in pyridine (100 c«c „) ethy lchl orof ormat e (2°9 g ») was added dropwise, and the mixture stirred and kept at ambient temperature for 72 hours e The pyridine was removed from the mixture by evaporation at reduced pressure, and the residual mixture distributed between water and methylene chloride 0 The aqueous layer was discarded and the methylene chloride solution washed solution of sodium hydroxide, and finally with water until the washings were neutral. After drying the methylene chloride solution over anhydrous sodium sulphate, and filtering to remove the solid, the methylene chloride was evaporated off and the residual oil distilled. 5~n-butyl-2-dimet]_ylamino- -etho^-carboi-yl was obtained as a colourless oil, b.p. 109*110 at 0*01 mm.

She following compounds were also obtained by the method of Example 3.

EXAMPLE 4 ~Me thy l^ -me thy 1 sulphonyl oxy-2-morpholino-pyrimidine, (Compound No. 19, Table I) having the formulas - was prepared as follows s~ 4~hydroxy"=6-methyl-2-morpholino-pyriirddine (4°87 g« p OQ25 mole) was suspended in dry dimethylformamide (25 ml.) and to the stirred suspension was added, all at onces 2 ml»s 0»025 mole of methane sulphonyl chloride. To the stirred mixture was added9 dropwise from a burette^ 3 *5 ml., 0°025 mole of triethylamine. The temperature of the reaction mixture rose to 42°C., and the mixture became almost clear.

Stirring was continued for 2 hours, the solution filtered, and the filtrate was poured into ice-water. The precipitated material was filtered off5 washed with a little ice-cold water, and dried. Recrystallisation from ethanol gave the product* 4°05 g« (68$) cup. 131°C.

The following compounds were also prepared by the method of Example 4· -n-Butyl-2-dimethyiamino-4~methyl-6-phenyl-carbonyloxypyrimidine, (Compound No. 10, Table i) having ~n-buty1-2-dimethylamino-4-hydroxy-6-methylpyrimidine ( *13 g , 0*02 mole)., anhydrous potassium carbonate (2*76 g«, 0*02 mole), benzoyl chloride (2*81 g., 0·02 mole) and ethyl acetate (50 ml..) was stirred and heated under reflux for 7 hours* The reaction mixture was left at room temperature overnight, the solvent removed in vacuo, and the residue taken up in toluene (100 ml.) .

The toluene was washed with ice-cold 5, aqueous sodium hydroxide solution, then with water until the washings were neutral, and finally dried (ligSO^). Removal of the toluene in vacuo left the product as a white crystalline solid (5*2 g~, 8¾g) which was recrystallised o from ethanol, s e 59 C« The above reaction was found to proceed satisfactorily in the solvents benzene, toluene,methyl ketone and acetonitrile^ Ethyl acetate was also a suitable solvent' In the following Examples the words: "LUBROL" , "AROMASOL" ,. wDISEERSOLw ,"LISSAPOL",,,CELL0FAS,, are Trade Marks* EXAMPLE 6 An emulsion concentrate was made up by mixing together the ingredients set out below in the proportions stated and stirring the mixture until all the constituents were dissolved* Compound No. 10 10 Ethylene Dichloride 0$ Calciumdodecylbenzene- sulphonate "Lubrol" L 10# "Aromase!" H 3f¾S EXAMPLE 7 A composition in the form of grains readily dispersible in a liquid, e.g. water, was prepared by grinding together the first three of the ingredients listed below in the presence of added water and then mixing in the sodium acetate. The resultant mixture was dried and passed through a British Standard mesh sieve, size 2*4-100, to obtain the desired size of grains.

Compound No. 10 5Q$5 "Dispersol" T 2¾£ "Lubrol" AP5 1·¾£ Sodium acetate 2 *5^ BXAMEDS 8 The ingredients listed below were all ground together in the proportions stated to produce a powder formulation readily dispersible in liquids.

Compound No. 10 45$ "Dispersol" T "Lissapol" NX 0·¾δ "Cellofas" B600 2$ Sodium acetate 47*5 EXAMPLE 9 The active ingredient (Compound No. 10 of Table i) was dissolved in a solvent and the resultant liquid was sprayed onto the granules of Fuller's earth. The solvent was then allowed to evaporate to produce a granular composition.

Compound No. 10 ¾£ Puller's earth or China clay granules 95 EXAMPLE 10 A composition suitable for use as a seed dressing was prepared by mixing all three of the substituents set out below in the proportions stated.

Compound No.10 59 Mineral oil 2$ China clay EXAMPLE 11 A dusting powder was prepared by mixing, in the proportions stated, the active ingredient with tale.

Compound No. 10 ¾2 Talc 3 EXAMPLE 12 A Col ormulation was prepared by ball-milling the constituents set out below and then forming an aqueous suspension of the ground mixture with water.

Compound No. 10 0$ "Dispersol" 10$ "Lubrol1 1% Water EXAMPLE 13 Formulations similar to those set out in Examples 6 Compositions according to the invention were made up in the following manner and tested against various fungal diseases, and the results of these tests are shown in Tables II and III hereinafter. In the tests both a protectant and an eradicant test were carried out, and in the protectant test the plants were sprayed so that the leaves were wetted with a solution or suspension containing 500 parts per million of the active compound and 0°1$ of a wetting agent, and after 2 hours were inoculated with the disease, the extent of which was assessed visually at the end of the teste In the eradicant test, the plants were inoculated with the disease and then sprayed (so that the leaves were wetted) after a number of days depending on the disease with a solution or suspension containing 500 parts per million of the aetive compound and 0°]$£ of a wetting agent* The results are shown in Table H below as a grading giving the percentage amount of disease as fallowst- Gradin^ Percentage Amount of Disease 0 61 to 100 1 26 to 60 2 6 to 25 3 0 to COMPOUND PUCCI IA PHYTOPHTHQRA SPHAEROTHECA EEYSIPHE ERYSIPHE PODO NO. RECONDITA INFESTANS FDLI&INEA &RA MINIS GRA MINIS LEUC (fiust) (Late Blight) ( Powdery (Powdery (Powder (Pow Mildew) Mildew) Mildew) Mil Wheat Tomato Cucumber Wheat Barley Ap 4 10 10 10 -1 Pr©t Era d Prot Erad Prot Erad Prot Erad Prot Erad Prot 1 0 0 0 - 3 - - - - - 2 0 0 0 - 3 3 3 3 3 3 0 0 0 - 3 1 0 0 1 - 3 3 2 - 2 - 1 0 0 2 - 3 2 6 0 0 3 - 3 2 - - - - - 7 0 0 2 - 3 3 8 1 0 2 - 3 3 3 - 3 - 3 9 1 0 2 - 3 3 3 - 3 - 20 2 0 2 - 3 3 3 - 3 - 3 11 0 0 2 - 2 2 12 1 0 3 - 3 3 13 0 0 3 - 3 3 14- - - *- 9 0 0 0 3 2 16 1 0 0 3 3 2 0 3 3 17 0 0 3 2 0 The toxicity of a number of the pyrimidine derivatives of this invention towards a vaiety of insect pests was investigated and the tests conducted and results obtained are set out below* The compounds of the invention were in each case used in the form o a liquid preparation containing Q*¾8! by weight of the compound. The preparations were made by dissolving each of the compounds in a mixture of solvents consisting of parts by volume of acetone and 1 part by volume o diaeetone alcohol. The solutions were then diluted with water containing 0·01 by weight of a wetting agent sold under the trade name of "LISSAPOL" NX until the liquid preparations contained the required concentration of the compound ("LISSAPOL" is a Trade Hark).

The test procedure adopted with regard to each test insect was basically the same and comprised supporting a number of the insects on seme medium which may be a host plant or some foodstuff on which the insect feeds, and treating either or both the insect and the medium with the preparations* The mortality of the insects was then assessed at periods varying from one to three days after the treatment* The results of the tests are given below in Table III* In this Table the first column indicates the compound used* Each of the subsequent columns indicates the name of the test insect, the host plant or medium on which it was supported, and the number of days which were allowed to elapse after treatment before assessing the percentage of insects which had been killed. The assessment is expressed in integers which range from 0 to 3. 0 represents less than 3QJS kill 1 w from 30- 9!?? * 2 · ® 50-90$ " w ever Hie concentration of the invention compound in the solutions used was 1,000 parts per million for all the pests except in the cases of Aedes aegy tjt and ffieloidegyne incognita when the concentration of the invention compound in the solution used was 100 parts per million.

TABLE III

Claims (3)

1. 27664/2 What we claim is: - A pyrimidine derivative having the formula: - or a salt thereof, 81 - wherein ¾ and ¾ represent hydrogen atoms, lower alkyl radicals, a halophenyl radical, a pi eridino radical, a morpholino radical or a 1-methyl piperazin- -yl radical; Ej represents a hydrogen atom, a lower alkyl radical or a phenyl radical; represents an atom of hydrogen or bromine, a lower alkyl, lower alkenyl, or benzyl radical, or a nitro group; X represents an atom of oxygen or sulphur and E^ is a carbonyl or sulphonyl group bearing directly, or through an atom of oxygen or sulphur, a lower alkyl radical, a lower alkenyl radical, a phenyl radical or a nitro-, halo-, lower alkyl-substituted phenyl radical, a pi eridino radical, a furyl radical, or a styryl radical* 1 A pyrimidine derivative as claimed in Claim wherein E^ and fi^ represent hydrogen, or lower alkyl radicals; fi^ represents hydrogen, a lower alkyl radical or a phenyl radical; represents an atom of bromine, a lower alkyl, lower alkenyl, or benzyl radical, and E^ is a carbonyl or sulphonyl group bearing a lower alkyl radical, a lower alkoxy radical, a lower alkylthio radical, a phenyl radical or a nitre-, lower alkyl- or halo-substituted phenyl radical, a phenyl thio radical, an alkenyl radical, an ar alkenyl radical or a piperidino or furyl radical, or a salt thereof.

2. A pyrimidine derivative as claimed in Claim A-i wherein and are hydrogen or lower alkyl radicals; L is a lower alkyl radical; E. is a 27664/2 lower alkyl radical having 2 to 6 carbon atoms; and Rg is a carbonyl or sulphonyl group bearing a lower alkyl radical,' a lower alkoxy radical, a phenyl radical or a styryl radical. (4) A pyrimldine derivative according to Claim 3 wherein R. and „ are both methyl radicals or 1 2 Rj is hydrogen and g is an ethyl radical 3 is a methyl radical R^ Is butyl or amyl radical; X is an atom of oxygen; and & is lower alkyl, lower alkoxy or phenyl radical. (5) Each of the pyrimldine derivatives set out hereinbefore in Table I. (6) S-n- butyl-2 -dimethylamino-4 -methyl -6 -phenyl - carbonyloxypyrimidine. (7) A process for making a pyrimldine derivative claimed in any of Claims 1 to 5 which compriseB reacting a compound of the formula: - wherein ^, Rg, Rg» 4 and X have any of the meanings stated in Claim 1 with acyl or sulphonyl halide of the formula:- c 27664/2 -Hal R5 wherein Rg haanany of the meanings stated in Claim 1 and Hal represents a halogen under conditions where the hydrogen halide which is formed is removed as it is produced. A process according to Claim 7 carried out in the presence of a diluent as a reaction medium . A process according to claim 8 wherein the diluent is a solvent for the reactants. A process as claimed in any of Claims 7 to 9 wherein the hydrogen halide is removed by carrying out the reaction in the presence of an add acceptor. A process as claimed in Claim 10 wherein the acid acceptor is a base or a salt of a strong base and a week acid. A process as claimed in Claim 11 wherein the acid acceptor is an alkali or alkaline earth metal hydroxide or carbonate. A process as claimed in claim 1 wherein the base is a tertiary amine. A process as claimed in claim 13 wherein the tertiary amine is triethylamine. 27664/2 A process as claimed in Claim 13 wherein the tertiary amine is pyridine. A process for making a pyrimidine derivative as claimed in any one of Claims 1 to 6, which comprises reacting the appropriate acyl or sulphonyl halide with a metallic salt of the appropriate 6 -hydroxy- or 6-mercapto pyrimidine, if necessary in the presence of a solvent. A biologically active composition comprising as active ingredient a pyrimidine derivative as claimed in any of Claims 1 to 6 and a diluent. A biologically active composition as claimed in Claim 17 wherein the diluent is a solid diluent. A biologically active composition as claimed in Claim 18 wherein the solid diluent Is an inert substance in powder or granular form. A biologically active composition as claimed in Claim 18 wherein the solid diluent is a powdered or granular fertiliser material. A biologically active composition as claimed in Claim 17 wherein the diluent is a liquid. A biologically active composition as claimed in Claim 21 wherein the liquid is water or an organic 27664/2 A biologically active composition as claimed in any of Claims 17 to 22 comprising a wetting agent. A biologically active composition ad claimed in any of Claims 17 to 23 comprising from 0. 001% to 85% by weight of the active ingredient. A biologically active composition as claimed in Claim 24 comprising from 10% to 85% by weight of the active ingredient. A biologically active composition as claimed in Claim 23 comprising from 0. 001% to 1. 0% by weight of the active ingredient. A method of combating undesired ; fungal infections in plants which comprises applying to the locus of the plant a pyrimidine derivative as claimed In any of Claims 1 to 6 or a composition as claimed in any of Claims 1 to 28. A method of combating undesired insect infestations in plants which comprises applying to the locus of the plant an insecticldally active pyrimidine derivative as claimed in any of Claims 1 to 6 or a composition as claimed in any of Claims 17 to 26 containing such a derivative. A method of combating plant pathogens which comprises applying to a plant or to seeds thereof* 27664/2 A method of treating agricultural eoil comprising applying to the soU a p rimidine derivative as claimed in any of Claims 1 to 6 or a composition &» claimed in any of Claims 17 to 26. A fertiliser comprising a pyrimidine derivative as claimed in any of Claims 1 to 6. Pyrimidine derivatives according to Claim 1 and processes for their preparation substantially as described, particularly with reference to the foregoing Examples 1 to 5. Biologically active compositions according to Claim 17 substantially as described, particularly with reference to the foregoing Examples 6 to 1

3. S. HOROWITZ & CO. AGENTS FOR THE APPLICANTS