GB2043061A

GB2043061A - Thienopyrimidine and quinazoline derivatives

Info

Publication number: GB2043061A
Application number: GB8004059A
Authority: GB
Original assignee: Imperial Chemical Industries Ltd
Current assignee: Imperial Chemical Industries Ltd
Priority date: 1979-03-05
Filing date: 1980-02-07
Publication date: 1980-10-01
Also published as: AR224640A1; GB2043061B

Abstract

Plant fungicidal, bactericidal, antiviral, insecticidal and growth regulating compounds are a thienopyrimidine or quinazoline derivative of the formula: <IMAGE> wherein R is a straight or branched chain alkylene group optionally substituted with a hydroxy group; Q is hydrogen, phenyl, cycloalkyl or a straight or branched chain alkyl group optionally substituted with one or more halogen atoms, or with an alkoxy- or alkoxyalkoxy-group; X is O, S or SO2; the number of carbon atoms in R and Q combined being from 5 to 18 when R is alkylene and from 3 to 18 when R is hydroxyalkylene; and optical isomers and salts thereof.

Description

SPECIFICATION Heterocyclic compounds and their use as pesticides This invention relates to methods of combating pests, especially fungal, viral and bacterial infections of plants, insect and acarina pests, by the use of certain thienopyrimidine and quinazoline derivatives; and to plant anti-fungal, anti-viral and anti-bacterial compositions; and to insecticidal and plant growth promoting compositions and to certain novel, specific, thienopyrimidine and quinazoline derivatives, and processes for making them.

The present invention provides thienopyrimidine and quinazoline derivatives having the general formulae:

wherein R is a straight or branched chain alkyl group optionally substituted with a hydroxy group; Q is hydrogen, phenyl, cycloalkyl or a straight or branched chain alkyl group optionally substituted with one or more halogen atoms, or with an alkoxy- or alkoxyalkoxy-group; X is 0, S or SO,; the number of carbon atoms in R and Q combined being from 5 to 18 when R is alkyl and from 3 to 1 8 when R is hydroxyalkyl; and optical isomers and salts thereof.

In a further, preferred, aspect the invention provides thienopyrimidine derivatives having the formula:

wherein R is a straight or branched chain alkyl group; Q is hydrogen; X is 0; the number of carbon atoms in R being from 5 to 18; and optical isomers and salts thereof.

More preferred compounds are those as defined in the preceding paragraph wherein the number of carbon atoms in R is from 5 to 8.

Also preferred are compounds of the formula:

wherein R is a straight or branched chain alkyl group; 0 is a straight or branched chain alkyl group optionally halo substituted; X is 0; the number of carbon atoms in R being from 4 to 7 and in Q from 2 to 3; and optical isomers and salts thereof.

Also preferred are compounds of formula:

wherein R is a straight or branched chain alkyl group; 0 is a straight or branched chain alkyl group optionally substituted with one or more halogen atoms or with an alkoxy or alkoxyalkoxy group; X is O or S; the number of carbon atoms in R being from 3 to 5 and in Q from 2 to 9; and optical isomers and salts thereof.

Specific examples of thienopyrimidine and quinazoline derivatives according to the invention are set forth in Table I below and correspond to the general formulae:

wherein R-X-Q is as shown in the Table. The invention includes all those specific, novel, chemical compounds listed in Table I hereinafter. TABLE I In the column headed nucleus : TP represents Q represents

COMPOUND NUCLEUS r-X-Q m.p. C [b.p. C NUMBER (bath)/mm Hg] 1 TP CH(CH3)(CH2)3OCH2CH3 90 2 Q CH(CH3)(CH2)3OCH2CH3 95 3 TP CH(CH3)(CH2)2OCH2CH3 68 4 TP CH(CH3)(CH2)3O(CH2)3CH3 69, (200/0.1) 5 TP CH(CH3)(CH2)2O(CH2)3CH3 (170/0.05) 6 TP CH(CH3)(CH2)3SCHE 97, (180/0.05) TABLE I CONTINUED...

COMPOUND NUCLEUS R-X-Q m.p. C [b.p. C NUMBER (bath)/mm Hg] 7 TP CH(CH3)CH2O(CH2)3CH3 (160/0.05) 8 TP CH(CH3)CH2OH 196 9 TP CH(CH2OH)(CH2)5CH3 102 10 TP CH(CH2OCH2CH3)(CH2)5CH3 (180/0.2) 11 TP CH(CH2OCH3)(CH2)5CH3 (175/0.1) 12 TP (CH2)3OCH2CH(CH2CH3)(CH2)3CH3 (200/0.08) 13 TP CH(CH3)(CH2)3O(CH2)2O(CH2)3CH3 (225/0.1) 14 TP CH(CH3)(CH2O(CH2)5CH3 60, (175/0.1) 15 TP CH(CH3)(CH2)3S(CH2)3CH3 (195/0.2) 16 TP CH(CH3)(CH2)3SO2CH3 (260/0.1) 17 TP CH(CH2OH)(CH2)7CH3 99 18 TP CH(CH2OH)CH(CH3)2 158 19 TP CH(CH2OH)C6H5 166 20 TP CH(CH2OH)(CH2)2CH3 125 21 TP CH(CH3)(CH2)3O(CH2)2CH3 103 22 Q CH(CH3)(CH2)3O(CH2)3CH3 84 23 Q CH(CH3)(CH2)3O(CH2)2O(CH2)2CH3 55, (205/0.1) 24 TP CH(CH3)CH2C(OCH3)(CH3)2 140 25 TP CH(CH3)CH2OC6H5 143 TABLE I CONTINUED....

COMPOUND NUCLEUS R-X-Q m.p. C [b.p. C NUMBER (bath)/mmHg] 26 TP CH(CH3)(CH2)3O(CH2)2O(CH2)2O(CH2)3CH3 (225/0.08) 27 TP CH(CH3)CH2O(CH2)2O(CH2)3CH3 (210/0.1) 28 TP CH(CH3)(CH2)3OH 108, (240/0.1) 29 Q CH(CH2OH)(CH2)5CH3 145 30 TP CH(CH3)(CH2)3C(OH)(CH3)2 -* 31 TP CH(CH3)CH(OH)CHE 126 32 TP CH(CH3)(CH2)3O(CH2)gCH3 (190/0.2) 33 TP CH(CH3)CH(CH3)O(CH2)5CH3 (170/0.4) 34 TP CH(CH3)(CH2)4O(CH2)2CH3 72, (180/0.02) 35 TP CH(CH3)(CH2)3O(CH2)2O(CH2)5CH3 (210/0.02) 36 TP CH(CH3)(CH2)5OCH2CH3 (160/0.1) 37 TP CH(CH3)(CH2)3O(CH2)5CH3 (210/0.4) 38 TP CH(CH2OH)CH2O(CH2)7CH3 92 39 TP p-dodecylbenzxene sulphonate salt of -* Compound No 13 40 TP dedecyl sulphate salt of -* Compound No 13 41 TP CH2CH2CH2-O-cyclohexyl 76 TABLE I CONTINUED....

COMPOUND m.p. C [b/p. C NUMBER NUCLEUS R-X-Q (bath)/mm Hg] 42 TP (CH2)3OCH(CH3)2 55 43 TP (CH2)2CH(CH3)O(CH2)2CH3 68 44 TP (CH2)3S(CH2)3CH3 56 45 TP (CH2)3O(CH2)3CH3 58 46 TP (CH2)2CH(CH3)OCH(CH3)2 86 47 TP (CH2)3SCH(CH3)2 71 48 TP (CH2)3OCH2CF3 97 49 TP (CH2)2O(CH2)2O(CH2)3CH3 -* 50 TP (CH2)3O(CH2)7CH3 -* 51 TP (CH2)3O(CH2)5CH3 56 52 TP (CH2)5OCH2CH3 -* 53 TP (CH2)3OCH2CCl3 116 54 TP (CH2)4O(CH2)2CH3 69 55 TP (CH2)3O(CH2)2OCH3 98 56 TP (CH2)3O(CH2)9CH3 -* 57 TP (CH2)6OCH3 69 58 TP (CH2)4OCH2CF3 79 TABLE I CONTINUED...

COMPOUND m.p. C [b.p. C NUMBER NUCLEUS R-X-Q (bath)/mm Hg] 59 TP (CH2)6OCH2CF3 75 60 TP (CH2)5OCH2CF3 68 61 TP (CH2)2CH(CH3)OCH2CF3 83 62 TP (CH2)3O(CH2)6CH3 57 63 TP (CH2)7OCH2CF3 -* 64 TP (CH2)3O(CH2)8CH3 103 *Where no melting/boiling point is recorded, the Compound was a gum/glass characterised by spectral and analytical methods.

Compounds Nos 8 and 31 of Table I are included as intermediates useful for preparing other compounds in the Table.

Any compound specifically mentioned in Table I but not in the Examples describing chemical synthesis was prepared by treating an amine, made by methods previously described in the literature, with 4-chlorothieno(2,3-d]pyrimidine in a manner similar to that described in the last stage of Example 1.

All these compounds are new and constitute specific compounds according to the present invention; and provide specific pesticidal processes using them to combat fungal, viral and bacterial diseases of plants and insect pests; and provide specific pesticidal compositions containing them; and the invention includes new and/or analogous processes as herein described for making them.

Particularly preferred compounds in Table I are those numbered 9, 17, 52, 54, 59 and 60 and these compounds are also particularly useful for combating insect and acarine pests which infest domestic and farm animals.

The compounds of the invention, both novel and known, can be made either by: (i) treating 4-chlorothieno[2,3-djpyrimidine or 4-chloroquinazoline with an appropriate amine.

The solvent may be e.g. ethanol, acetonitrile, toluene and the base e.g. triethylamine, or (ii) treating a 4-alkylamino-thieno(2,3-d]pyrimidine or a corresponding quinazoline, substituted in the alkyl function with a hydroxyl group, with an alkylating agent such as an alkyl bromide, alkyl iodide or dialkyl sulphate. The solvent may be e.g. N,N-dimethylformamide and the base may be e.g. sodium hydride.

The thienopyrimidine and quinazoline derivatives, and compositions containing them, are variously active against many fungal pathogens of plants and seeds including, for example, Phycomycetes, Ascomycetes, Basidiomycetes, and Fungi Imperfecti. The following diseases are specifically mentioned by way of example: Erysiphe graminis (powdery mildew) on wheat and barley.

Botrytis cinerea (grey-mould) on tomatoes, vines, strawberries and other crops.

Venturia inaequalis (scab) on apples.

Puccinia recondita (rust) and other Puccinia species on cereals, and rusts on coffee and other hosts.

Phytophthora infestans (late blight) on tomatoes and potatoes.

Plasmopara viticola (downy mildew) on vines.

Uncinula necator(powdery mildew) on vines.

Piricularia oryzae (blast) on rice.

Podosphaera leucotricha (mildew) on apples.

The invention compounds also display a broad spectrum of anti-fungal and anti-bacterial activity in vitro and are likely to be active against all main groups of these pathogens.

Compound No 34 of Table I is, for example, particularly active against the plant fungal disease Piricularia oryzae (rice blast). They also exhibit growth regulating effects on plants.

The present invention further provides a process for combating fungal, viral and bacterial diseases of plants and insect and acarina pests which comprises applying to plants or animals, or to the locus of plants or animals, an antifungal, anti-viral, anti-bacterial, insecticidal or acaricidal amount of a thienopyrimidine or quinazoline as defined in any of the preceding paragraphs.

The thienopyrimidine and quinazoline derivatives and compositions containing them also display properties influencing and regulating the growth of plants, and the present invention includes their deployment for this purpose.

The invention further provides a process for regulating the growth of plants which comprises applying to plants, or to the locus of plants, a thienopyrimidine or quinazoline derivative as defined in any of the preceding paragraphs.

A particularly valuable feature of the activity of these derivatives is their systemic effect, i.e.

their ability to move in a plant to combat an infection or infestation remote from the site of initial application. Thus a derivative, or a composition containing it, may be applied to the soil surrounding the roots of a plant or to the seed or to other plant areas, e.g. leaves, and be taken up by the plant through its roots, or other areas, to combat fungi locally or elsewhere on the plants.

The invention compounds also display broad spectrum acaricidal and insecticidal activity including activity against red spider mites (adults and eggs), aphids, californian red scale, flies, caterpillars and beetles. The compounds, and compositions containing them, have shown themselves to be particularly useful in combating insect and acarine pests which infest domestic animals, such as Lucilia sericata, and ixodid ticks such as Boophilus spp. (e.g. Boophilus microplus), Ixodes spp., Amblyomma spp., Rhipicephalus spp., and Dermaceutor spp.They are effective in both susceptible and resistant strains of these pests in their adult, larval and intermediate stages of growth, and may be applied to the infested host animal by topical, oral or parenteral administration, using formulations well known in the art for such purpos'es.

In Australia, as well as in other countries, a problem of considerable economic importance is the control of ticks which infest cattle. In the past "susceptible" or non-resistant" strains of ticks have been controlled by means of sprays or dips using as active ingredients certain chemicals such as carbamates, chlorinated hydrocarbons or organophosphates. However more recently it has been found that certain strains of cattle ticks have emerged and are now wide spread in Australia and elsewhere and are spreading further and which are not affected by certain of the broad spectrum tickicides normally used for this purpose. These strains are known as "resistant" strains of cattle ticks and represent a most serious problem to the Australian cattle industry.

A typical "susceptible" strain is the "Yeerongpilly" strain which is widely distributed and is controlled readily with commercial tickicides such as l-naphthyl N-methylcarbamate, dichlorodiphenyltrichloroethane (DDT) or a wide range of organophosphorus tickicides including those available commercially under the registered trade names of "Asuntol", "Dioxathion", "Durs ban", "Ethion", "Nexagan" S or "Solgard". It is used by all authorities in Australia as the "susceptible" reference standard against which the degree of resistant strains is measured.

A typical resistant strain is the "Biarra" strain also known as the "Esk" or "Anderson" strain, and it has become increasingly resistant to organophosphorus tickicides with the passage of time since it was isolated in the Esk district of Queensland, Australia in 1 966. Other strains of cattle tick which are resistant to organophosphorus tickicides include the so called "Mount Alford" strain and the "Mackay" strain. Certain strains of cattle tick may become resistant to treatment with tickicides after prolonged treatment therewith. For example whilst DDT was effective as a tickicide when it was first used for the purpose, there are now strains of tick which are immune to treatment with DDT at concentrations which are economic.It is highly desirable that new tickicides be developed so that the cattle tick has little or no resistance to the tickicides when it is first used. Such tickicides should be effective in controlling and killing cattle ticks of both the "susceptible" strains and the strains which are resistant to tickicides already in use.

Unless a tickicides is active against both the "resistant" and "susceptible" strains, the long range effect of treatment in a given treatment area is not to control cattle ticks, but merely to increase the population of the "resistant" strain in relation to that of the "susceptible" strain.

Accordingly the invention further provides a process for the control or eradication of ticks which process comprises applying to a media infested with ticks an effective amount of a thienopyrimidine or quinazoline derivative as defined in any of the preceding paragraphs, or a composition containing such a derivative, as hereinafter described.

In a particularly preferred aspect the invention provides a process for the control or eradication of cattle tick (Boophilus microplus) which process comprises applying to said cattle tick or media infested with said cattle tick an effective amount of a thienopyrimidine or quinazoline derivative as defined in any of the preceding paragraphs; or a composition containing such a derivative as hereinafter described.

By the term "media" is intended buildings, and animals such as horses, sheep, dogs and cattle. The invention process is particularly useful for the treatment of cattle to control infestations of cattle tick.

Accordingly the invention further provides a process for the treatment of cattle which process comprises treating cattle infested with, or liable to be infested with, cattle tick (Boophilus microplus) with a tickicidally effective amount of a thienopyrimidine or quinazoline derivative as defined in any of the preceding, or subsequent paragraphs, or a composition containing such a derivative, as hereinafter described.

The invention process produces high contact activity against various strains of Boophilus microplus in the adult, larval and intermediate stages and both "susceptible" and "resistant" strains may be controlled by its use. The simultaneous efficacy against both "susceptible" and "resistant" strains of Boophilus microplus is of considerable and increasing economic importance.

The thienopyrimidine and quinazoline derivatives may be used as fungicides, viricides, bactericides, insecticides, acaricides or tickicides alone, but are preferably incorporated in compositions comprising a diluent in addition to the thienopyrimidine or quinazoline derivative.

In a further aspect, therefore, the invention provides plant anti-fungal, anti-viral, anti-bacterial, insecticidal, acaricidal and tickicidal compositions comprising as an active ingredient a thienopyrimidine or quinazoline derivative, or an optical isomer or a salt thereof, as defined in any of the preceding paragraphs; together with a carrier for the active ingredient; and optionally, a surfaceactive agent.

For the control of fungal, viral and bacterial infections of plants, the rate at which the thienopyrimidine and quinazoline compounds of the invention are applied will vary, depending upon the particular compound chosen for use, the disease to be controlled and on the particular species of plant acting as host to the disease.

In carrying the invention process into practical effect the growing crops, plants, seeds or soil may be treated by any of the well known and established procedures used in agriculture and crop protection. Thus, for example, the active compound may be applied as solids, e.g. powders or granules, or as liquids, e.g. solutions, dispersions, emulsions and these may comprise, in addition to the active substance, any other adjuvant, for example stickers, adjuvants specifically useful for formulation purposes, or any other biologically active substance, for example to increase the number of diseases combated, or having other desirable properties.

Such solid or liquid substances and formulations may be applied, for example, by any conventional technique, for example, by dusting, or otherwise applying the solid substances and formulations to the surfaces of growing crops, harvested produce, plants, seeds or soil, or to any part, or combination of parts, thereof, or, for example, by applying liquids or solution, for example, by dipping, spraying, mist-blowing or soaking techniques.

The invention process is therefore useful for treating plants, seeds, harvested fruits, vegetables, or cut flowers infested with, or liable to infestation with any of the aforementioned specific fungal or bacterial diseases.

The term "seeds" is intended to include propagative plants forms generally and therefore includes, for example, cut stems, corms, tubers, rhizomes and the like.

As previously noted the thienopyrimidine and quinazoline derivatives are preferably used in admixture with a solid or liquid diluent. The admixtures so obtained are hereinafter referred to as compositions. Preferably the compositions comprise a surface-active agent.

The solid compositions may be, for example, in the form of dusting powders, or may take the form of granules. Suitable solid diluents include, for example kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia and Fuller's earth.

Solid 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.

Liquid comositions include aqueous solutions, dispersions and emulsions containing the active ingredient preferably in the presence of one or more surface-active agents. Water or organic liquids may be used to prepare solutions, dispersions, or emulsions of the active ingredient. The liquid compositions of the invention may also contain one or more corrosion inhibitors for example lauryl isoquinolinium bromide.

Surface-active agents may be of the cationic, anionic or non-ionic type. Suitable agents of the cationic type include, for example, cetyltrimethyl ammonium bromide. Suitable agents of the anionic type include, for example, soaps, salts of aliphatic monoesters of sulphuric acid, for example sodium lauryl sulphate; and salts of sulphonated aromatic compounds, for example, dodecylbenzene-sulphonate, sodium, calcium and ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of the sodium salts of diisopropyl- and triisopropyl-naphthalenesulphonic acid. Suitable agents of the non-ionic type include, for example, the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol and 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 acids and hexitol anhydrides, for example sorbitol monolaurate, and the condensation products of the said partial esters with ethylene oxide and lecithins.

The compositions which are to be used in the form of aqueous solutions, dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use. These concentrates are usually 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 homogenous for a sufficient time to enable them to be applied by conventional spray equipment. In general concentrates may conveniently contain from 10 to 85% and preferably from 25 to 60% by weight of active ingredient. One suitable form of concentrate is an emulsifiable concentrate comprising a solution of thienopyrimidine or quinazoline derivative, as defined above, in an organic solvent containing a surface-active agent.When required for use, the concentrate can readily be dispersed in water by agitation to provide a dilute emulsion suitable for spraying.

Dilute preparations ready for use may contain varying amounts of the active ingredient, depending upon the purpose for which they are to be used; however, dilute preparations may contain between 0.0005% and 0.1% by weight of the active ingredient.

It is to be understood that the pesticidal compositions used in this invention may comprise, in addition to one or more thienopyrimidine or quinazoline derivatives, one or more other compounds having biological activity.

Suitable dose rates of the active ingredient for the control of infestations of cattle tick on cattle are not narrowly critical and are dependent to some extent on the strain of tick being treated.

Rates will also be related to the mode of application of the active ingredient, for example the rate will vary for each type of application such as dipping, spraying or dusting of the infested surface. As a general guide dips containing up to 5% w/w of active ingredient are satisfactory for most degrees of severity of infestation by "resistant" strains of tick and adequate control may be effected in many instances where the concentration of active ingredient in a dip is in the range from 0.005% to 1.0% w/w.

The invention is illustrated, but not limited, by the following Examples, in which degrees of temperature signified by " are expressed in degrees Centigrade. Examples 1 to 1 3 are related to processes for the preparation of thienopyrimidine or quinazoline derivatives; Examples 14 to 22 to pesticidal compositions; and the remaining Examples to processes for combating fungi, viruses, bacteria or insect pests, including ticks.

EXAMPLE 1 This Example illustrates the preparation of Compound Nos 3 and 5 of Table I.

2-Ethoxyethyl bromide (36.0 g) was added slowly to a solution of diethylmethylmalonate (41.2 g) and sodium ethoxide (from 5.44 g sodium) in ethanol (116 ml). The solution was refluxed for six hours, evaporated to dryness and the residue treated with water and dilute hydrochloric acid, then extracted with ether. The extract was washed with brine, dried, evaporated and distilled to give diethyl 2(2-ethoxyethyl)-2-methyl-malonate (37.38 g, b.p.

94-98"/1.5 mm).

A mixture of this material, potassium hydroxide (62 g), water (60 ml) and ethanol (22 ml) was refluxed for two hours and the ethanol removed in vacuo. It was then cooled in ice, acidified with 50% sulphuric acid, and extracted with ether. The extracts were dried, evaporated and distilled to give 4-ethoxy-2-ethylbutyric acid (13.43 g, b.p. 94-96"/3 mm).

A mixture of this material (6.18 g), chloroform (50 ml) and concentrated sulphuric acid (14.5 g) was vigorously stirred and heated to 41", then treated portionwise with sodium azide (3.3 g) maintaining the temperature at 38-40". It was heated at 50-55" for six hours, cooled and the aqueous phase removed, cooled in ice, basified with sodium hydroxide solution (50% w/v) and steam distilled. The distillate was acidified with sulphuric acid, evaporated to dryness in vacuo and the residue treated with sodium hydroxide solution (50% w/v) and extracted with ether.

The extracts were dried, evaporated and distilled to give 3-ethoxy-1-methylpropylamine (1.04 g, b.p. 137-139").

A mixture of this material (1.04 g), 4-chlorothieno-[2,3-d]pyrimidine (1.5 g), triethylamine (1.8 g) and ethanol (7.5 ml) was refluxed for three hours, cooled and extracted with ether. The extracts were washed with water and brine, dried and evaporated to give an oil (2.1 2 g) which crystallised on scratching. Rectystallisation from cyclohexane/petroleum (b.p. 40-60") gave Compound No 3 of Table 1(1.19 g, m.p. 68 ).

Compound No 5 of Table I was prepared similarly, using 2-butoxyethyl bromide in place of 2ethoxyethyl bromide in the first stage of the procedure.

EXAMPLE 2 This Example illustrates the preparation of Compound Nos 1, 2, 4 and 22 of Table I.

2-Ethoxyethyl bromide (41.8 g) was added dropwise over 45 minutes to a stirred and gently refluxing mixture of ethyl acetoacetate (32.5 g) and sodium ethoxide (from 5.75 g sodium) in ethanol (125 ml). After refluxing for a further ten hours, the mixture was cooled, filtered and the filtrate evaporated and distilled to give ethyl 2(2-ethoxyethyl)-3-ketobutyrate (20.8 g, b.p.

115-122"/12 mm).

A mixture of this material (30.9 g), sodium hydroxide solution (5N, 38.2 ml) and water (11 5 ml) was stirred for four hours at room temperature, filtered and the filtrate treated with aqueous sulphuric acid (50% v/v, 1 6 ml). It was then heated at atmospheric pressure until 60 ml of distillate was collected. This was extracted with dichloromethane and the extracts washed with sodium bicarbonate solution and water, dried, evaporated and distilled to give 5-ethoxy-pentan2-one (11.5 g, b.p. 80-81"/30 mm).

A mixture of this material (11.44 g), formamide (14 ml) and formic acid (11.8 ml) was heated for eight hours at 170-180", cooled and poured into water (30 ml) containing excess potassium carbonate. The resultant oil was separated, treated slowly with ice-cooling with concentrated hydrochloric acid (10 ml), then heated on a steam bath for 75 minutes. The solution was icecooled, basified with potassium hydroxide, extracted with ether, and the extracts washed with brine, dried over potassium hydroxide, evaporated and distilled to give 2-amino-5-ethoxypentane (2.78 g, b.p. 74-78"/32 mm).

This material (1.55 g) was treated with 4-chlorothieno[2,3-djpyrimidine (2.0 g), in a similar manner to that described in the final stage of Example 1, to give Compound No 1 of Table I (1.99 g, m.p. 90 ).

Compound No 4 of Table I was prepared similarly, using 2-butoxyethyl bromide in place of 2ethoxyethyl bromide in the first stage of the procedure.

Compound Nos 2 and 22 were prepared in a similar fashion by reacting the appropriate amine with 4-chloroquinazoline using triethylamine as base and toluene and acetonitrile respectively as solvents.

EXAMPLE 3 This Example illustrates the preparation of Compound Nos 13, 21, 23, 26 and 37 of Table I and also provides an alternative procedure to that described in Example 2.

2-Butoxyethanol (2.5 g) was added dropwise, with cooling, to a stirred suspension of sodium hydride (50%, 1.92 g, prewashed with petroleum, b.p. 40-60") in N,N-dimethylformamide (6 ml). The mixture was stirred for 1 5 minutes, then treated dropwise with 5-chloro-pentan-2-one ethylene ketal (3.21 g). It was allowed to stir overnight at room temperature, poured on to ice/water and extracted with ether. The extracts were washed with brine, dried, evaporated and distilled in a bulb-tube apparatus to give 5(2-butoxyethoxy)-pentan-2-one ethylene ketal [2.45 g b.p. 96-98" (bath)/0.08 mm].

A mixture of this material, formamide (1.5 ml) and formic acid (1.5 ml) was heated at 180 for five hours, cooled, and added to water (8 ml) containing excess potassium carbonate. The oil was separated, treated with concentrated hydrochloric acid (1.5 ml) whilst maintaining the temperature at ca 20 , and heated on a steam bath for 75 minutes. It was then cooled, basified with aqueous potassium hydroxide solution and extracted with ether. The extracts were washed with water, dried, evaporated and distilled in a bulb-tube apparatus to give 2-amino-6,9dioxatridecane [0.9 g, b.p. 153-158" (bath)/15 mm].

This material (0.76 g) was treated with 4-chlorothienopyrimidine (0.64 g), triethylamine (0.81 g) and ethanol, in a similar manner to that described in the final stage of Example 1, to give Compound No 13 of Table I [0.95 g, b.p. 223 (bath)/0.1 mm].

Compound Nos 21, 26 and 37 of Table I were prepared similarly, using the appropriate alcohols in place of 2-butoxyethanol in the first stage of the procedure.

Reaction of 2-amino-6,7-dioxatridecane with 4-chloroquinazoline in acetonitrile in the presence of triethylamine, in a manner similar to that described in the final stage of Example 1, gave Compound No 23 of Table I.

EXAMPLE 4 This Example illustrates the preparation of Compound Nos 6 and 1 5 of Table I.

A mixture of butanethiol (11 ml), sodium ethoxide (from 2.3 g sodium), ethanol (100 ml) and 5-chloropentan-2-one ethylene ketal (13 ml) was refluxed for ten hours, cooled and evaporated.

The residue was extracted with ether and the ethereal solution evaporated to give 5-butylthiopentan-2-one ethylene ketal (18.2 g).

This material was treated with formamide (15 ml) and formic acid (13 ml) as described for a related compound in Example 3 to give 2-amino-5-butylthiopentane (6.66 g, b.p.

124-129"/14 mm).

Further reaction of this material (1.5 g) with 4-chlorothieno[2,3-d]pyrimidine (1.5 g) in ethanol containing triethylamine, in a similar manner to that described in the final stage of Example 1, afforded Compound No 1 5 of Table I [2.2 g, b.p. 195 (bath)/0.2 mm].

Compound No 6 of Table I was prepared similarly, using methanethiol in place of butanethiol in the first stage of the procedure.

EXAMPLE 5 This Example illustrates the preparation of Compound No 16 of Table I.

A stirred mixture of Compound No 6 of Table 1(2.5 g), acetic acid (10 ml) and sulphuric acid (1 N, 20 ml) was cooled in ice and treated with potassium permanganate (2.0 g). It was stirred vigorously for 45 minutes, diluted with water, decolourised with excess sodium metabisulphite, neutralised with sodium bicarbonate solution and extracted with dichloromethane. The extracts were washed with water, dried, evaporated and distilled in a bulb-tube apparatus to give Compound No 16 of Table 1 [0.99 g, b.p. 260 (bath)/0.1 mm].

EXAMPLE 6 This Example illustrates the preparation of Compound Nos 34 and 36 of Table I.

A steady stream of chlorine was passed for 2 hours, at 5-10", into a stirred suspension of 1methylcyclopentanol (37.5 g) in water UOO ml) and sodium hydroxide (30 g). The mixture was extracted with dichloromethane and the extracts washed carefully with sodium bicarbonate solution and water and dried over magnesium sulphate. The dichloromethane solution was refluxed for 40 minutes, evaporated and distilled to give 6-chlorohexan-2-one (37.5 g b.p.

87-88"/17 mm).

A mixture of this material (24.8 g), ethylene glycol 14 g), p-toluenesulphonic acid (0.5 g) and toluene (200 ml) was refluxed, using a Dean-Stark trap, for 3+ hours. It was then cooled, poured into a mixture of ice-water (400 g) and sodium carbonate (20 g) and extracted with ether. The extracts were washed with ice-cold water, dried over calcium chloride, evaporated and distilled to give 6-chlorohexan-2-one ethylene ketal (29.98 g, b.p. 52-58"/0.3 mm).

Sodium hydride (50%. 1.0 g) was treated dropwise, at O"C, with propanol (15 ml). After 1 5 minutes 6-chlorohexan-2-one ethylene ketal (3.6 g) was added and the mixture heated on a steam bath for 11 hours. Hydrochloric acid (2N, 5 ml) was added and heating continued for a further 2 hours. The mixture was evaporated at 40 and the residue distributed between ether and water. The extracts were washed with sodium bicarbonate solution and water, dried, evaporated and distilled in a bulb-tube apparatus to give 6-propoxyhexan-2-one [2.2 g, b.p.

120-140 (bath)/ 1 7 mm]. A solution of this material in 5N methanolic ammonia (7 ml) was added to Raney Nickel (prepared according to Fieser and Fieser, Reagents for Organic Synthesis, Vol l, from 5 g of nickel-aluminium alloy) and vigorous stirring continued for 5 hours. The mixture was allowed to stand overnight, filtered through Supercel (finely divided silica), evaporated to dryness and the residue again dissolved in ether, filtered and evaporated to give 2-amino-5-propoxyhexane (1.78 g).A mixture of this material (1.1 g), 4-chlorothieno[2,3 d]pyrimidine (1.0 g), triethylamine (1.5 ml) and ethanol (10 ml) was treated in a manner similar to that described in the final stage of Example 1 to give Compound No 34 of Table 1(0.77 g, m.p. 72").

Compound No 36 was prepared using a similar sequence of reactions replacing 1-methylcyclopentanol by 1-methylcyclohexanol in the first stage, and sodium hydride/propanol by sodium/ethanol in the third stage, of the preparation.

EXAMPLE 7 This Example illustrates the preparation of Compound Nos 28, 32 and 35 of Table I and also provides an alternative procedure to those described in Examples 2 and 3.

A solution of 5-hydroxypentan-2-one (13.5 g) in 5N methanolic ammonia (60 ml) was added to Raney Nickel (prepared form 45 g alloy, see Example 6) and vigorous stirring continued for 1 8 hours. The mixture was filtered through Supercel, evaporated and the residue redissolved in methanol, filtered, evaporated and distilled to give 2-amino-5-hydroxypentane (9.0 g, b.p.

110-118"/15 mm).

A mixture of this material (6.0 g), 4-chlorothieno-[2,3-d]pyrimidine (9.0 g), trieth,ylamine (15 ml) and ethanol (50 ml) was refluxed for 1 8 hours, evaporated in vacuo, diluted with water, acidified with 2N hydrochloric acid, filtered through Supercel, basified with 5N sodium hydroxide solution and extracted with chloroform. The extracts were dried and evaporated to give a gum (9.0 g) which later crystallised. Recrystallisation from acetonitrile (charcoal) gave Compound No 28 of Table 1(4.4 g, m.p. 108 ).

This material (1.2 g) was added to a stirred suspension of sodium hydride (280 mg, 50%, prewashed with petroleum, b.p. 40-60") in N,N-dimethylformamide (10 ml). After 20 minutes at room temperature, decyl bromide (1.15 ml) was added and stirring continued overnight. The mixture was diluted with water and extracted with ether. The extracts were washed with water and brine, dried, evaporated and distilled in a bulb-tube apparatus to give Compound No 32 of Table 1 [0.90 g, b.p. 190 (bath)/0.02 mm].

Compound No 35 of Table I was made similarly, using 2-hexyloxyethyl bromide in place of decyl bromide in the final stage of the preparation.

EXAMPLE 8 This Example illustrates the preparation of Compound Nos 8, 9, 17, 18, 19, 20, 29, 31 and 38 of Table I.

Sulphuryl chloride (12 ml) was added dropwise over 30 minutes, maintaining the temperature below 10 , to a stirred mixture of oct-1-ene (24 ml) and acetonitrile (50 ml). The mixture was stirred for a further hour and evaporated in vacua The residue was treated with ice-water and concentrated hydrochloric acid, refluxed for 3 hours (allowing steam distillation), evaporated to dryness and dried by azeotroping with ethanol. Re-evaporation, trituration with ether and recrystallisation from isopropanol gave 2-aminooctanol hydrochloride (6.1 g).

A mixture of this material (5.0 g), 4-chloro[2,3-d]thienopyrimidine (4.75 g), triethylamine (12.

5 ml) and ethanol (37.5 ml) was refluxed for 3 hours, cooled, diluted with water and the resultant solid recrystallised from acetonitrile to give Compound No 9 of Table 1(4.9 g, m.p.

102").

Compound Nos 17, 18, 19, 20, 31 and 38 were made similarly, substituting the appropriate olefin for octene in the first stage of the preparation.

Compound No 8 utilised a modified procedure using propene and acetonitrile, with bromine in place of sulphuryl chloride.

Compound No 29 was prepared by reacting 2-amino-octanol hydrochloride, prepared as shown, with 4-chloro-quinazoline in acetonitrile using triethylamine as base.

EXAMPLE 9 This Example illustrates the preparation of Compound Nos 7, 10, 11, 14, 27 and 33 of Table I.

To a stirred ice-cooled suspension of sodium hydride (100%, 250 mg) in N,N-dimethylformamide (30 ml) was added Compound No 8 of Table 1(2.0 9, prepared as described in Example 8). After 20 minutes, 1-bromohexane (1.6 ml) was added and stirring continued for 18 hours at room temperature. The mixture was diluted with water and extracted with 50:50 ether:cyclohexane. The extracts were washed with water and brine, dried, evaporated and distilled in a bulb-tube apparatus to give Compound No 14 [1.7 g, b.p. 175 (bath)/0.1 mm; crystallised on standing, m.p. 60 ].

Compound Nos 7, 10 and 27 of Table I were made similarly, substituting the appropriate alkyl bromide or iodide for bromohexane. Compound No 33 additionally utilised Compound No 31 rather than Compound No 8 as an intermediate.

In the case of Compound No 11 of Table I, it was found necessary to use dimethylsulphate rather than methyl iodide since the latter gave rise to concomitant N-methylation.

EXAMPLE 10 This Example illustrates the preparation of Compound No 24 of Table I.

4-Methoxy-4-methyl pentan-2-one (5.8 g) was converted into 2-amino-4-methoxy-4-methylpentane (2.8 g) by treatment with Raney Nickel/ammonia/methanol in a manner similar to that described in Example 6. This amine (2.34 g) was treated with 4-chlorothieno[2,3-d]pyrimidine (1.75 g) in a manner similar to that described in the final stage of Example 1 to give Compound No 24 of Table 1(1.25 g, m.p. 140 ).

EXAMPLE 11 This Example illustrates the preparation of Compound No 30 of Table I.

A mixture of 4-chlorothieno[2,3-d]pyrimidine (2.0 g), 2-amino-6-hydroxy-6-methylheptane hydrochloride (2.3 g), triethylamine (5 ml) and ethanol (15 ml) was refluxed for 4 hours, cooled, diluted with water and extracted with ether. The extracts were themselves extracted with 2N hydrochloric acid and this extract basified and extracted with dichloromethane. The dichloromethane layer was washed, dried and evaporated to give a crude sample (2.48 g) of Compound No 30 of Table I.

Purification was achieved according to the following sequence: heating with 2N hydrochloric acid, evaporating to dryness, dissolving in chloroform, isolating basic material by extraction, recrystallising this intermediate from acetonitrile, hydrolysing by heating with 2N hydrochloric acid and isolation of basic material. Spectral and analytical data of this glass solid were in accordance with the proposed structure and with a high degree of purity.

EXAMPLE 12 This Example illustrates the preparation of Compound Nos 12 and 41-64 of Table I.

To cyclohexanol (100 g) and potassium t-butoxide (1.0 g) under nitrogen was added with stirring, over 40 minutes, acrylonitrile (60.2 g). The reaction mixture was stirred overnight, acidified with hydrochloric acid, added to water (600 ml) and extracted with dichloromethane.

The extracts were washed, dried, evaporated and distilled to give 2-cyclohexyloxypropionitrile (110.8 g, b.p. 126-128"/14 mm).

This material (76.5 g), anhydrous ammonia (100 g) and Raney Nickel (5 g) were charged to a Bergius bomb, pressurised to 21 8 atmospheres with hydrogen, warmed to 100" and maintained thus until hydrogen absorption ceased (24 hours). After cooling, the product was washed from the bomb with methanol, filtered, evaporated and distilled to give 3-cyclohexyloxypropylamine (56.0 g, b.p. 96-97"/14 mm).

This material was treated with 4-chlorothieno(2,3-d]pyrimidine, triethylamine and ethanol in a manner similar to that described in the final stage of Example 1 to give Compound No 41 of Table I.

Other compounds of this Example were made, for example, by treating the appropriate unsaturated nitrile (e.g. acrylonitrile, allyl cyanide, crotononitrile) or -halonitrile (e.g. 6-bromocapronitrile, 4-chlorobutyronitrile) with an alkoxide or thiolate anion; reducing the product with e.g. hydrogen in the presence of a suitable catalyst, or lithium aluminium hydride/aluminium chloride; and treating the amine so produced with 4-chlorothieno[2,3-d]pyrimidine in a manner similar to that described in Example 1. Physical constants are shown in Table I.

EXAMPLE 13 This Example illustrates the preparation of Compound Nos 39 and 40 of Table I.

A stirred mixture of Compound No 1 3 of Table 1(364 mg, prepared as described in Example 3) in 1 N hydrochloric acid (1 ml) was treated with a solution of sodium dodecylsulphate (288 mg) in water (5 ml). After 10 minutes, the mixture was extracted with dichloromethane and the extracts dried and evaporated to give Compound No 40 of Table I. Elemental analysis and spectral data showed the crude product to be of high purity and to have the structure shown.

Compound No 39 of Table I was made similarly, using sodium p-dodecylbenzene sulphonate in place of sodium dodecylsulphate.

EXAMPLE 14 An emulsifiable 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 1 of Table I 10% Ethylene dichloride 40% Calcium dodecylbenzenesulphonate 5% "Lubrol" L 10% "Aromasol" H 35% EXAMPLE 15 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 44-100, to obtain the desired size of grains.

Compound No 5 of Table I 50% "Dispersol" T 25% "Lubrol" APN 5 1.5% Sodium acetate 23.5% EXAMPLE 16 The ingredients listed below were all ground together in the proportions stated to produce a powder formulation readily dispersible in liquids.

Compound No 34 of Table I 45% "Dispersol" T 5% "Lissapol" NX 0.5% "Cellofas" B600 2% Sodium acetate 47.5% EXAMPLE 1 7 The active ingredient (Compound No 9 of Table I) was dissolved in a solvent and the resultant liquid was sprayed on to the granules of Fuller's earth. The solvent was then allowed to evaporate to produce a granular composition.

Compound No. 34 of Table I 5% Fuller's earth of China clay 95% granules EXAMPLE 18 A dusting powder was prepared by mixing, in the proportions stated, the active ingredient with talc.

Compound No 34 of Table I 5% Talc 95% EXAMPLE 19 A col formulation was prepared by ball-milling the constituents set out below and then forming an aqueous suspension of the ground mixture with water.

Compound No 34 of Table I 40% "Dispersol" T 10% "Lubrol" APN5 1% Water 49% EXAMPLE 20 A dispersible powder formulation was made by mixing together the ingredients set out below and then grinding the mixture until all the constituents were thoroughly mixed.

Compound No 34 of Table I 25% "Aerosol" OT/B 2% "Dispersol" A.C. 5% China clay 28% Silica 40% EXAMPLE 21 This Example illustrates the preparation of a dispersible powder formulation. In each instance all the ingredients are mixed ih the proportions stated and the mixture then ground in a comminution mill.

Compound No 34 of Table I 25% "PERMINAL" BX 1% "Dispersol" T 5% Polyvinylpyrrolidone 10% Silica 25% China clay 34% EXAMPLE 22 The ingredients set out below were formulated into a dispersible powder by mixing and grinding the ingredients in the proportions stated.

Compound No 34 of Table I 25% "Aerosol" OT/B 2% "Dispersol" T 5% China clay 68% Exactly the same formulations as set out in Examples 14 to 22 were prepared using the remaining Compounds of Table I.

In Examples 14 to 22 above percentage amounts are on a weight basis.

The following constitutes an explanation of the compositions or substances represented by the various Trade Marks and Trade Names referred to in the foregoing Examples.

"LUBROL" L is a condensate of 1 mole of nonyl phenol with 1 3 molar proportions of ethylene oxide.

"AROMASOL" H is a solvent mixture of alkylbenzenes.

"DISPERSOL" T AND AC is a mixture of sodium sulphate and a condensate of formaldehyde with the sodium salt of naphthalene sulphonic acid.

"LUBROL" APN5 is a condensate of 1 mole of nonyl phenol with 5+ moles of naphthalene oxide.

"CELLOFAS" B600 is a sodium carboxymethyl cellulose thickener.

"LISSAPOL" NX is a condensate of 1 mole of nonyl phenol with 8 moles of ethylene oxide.

"AEROSOL" OT/B is a dioctyl sodium sulpho succinate.

"PERMINAL" BX is an alkyl naphthalene sulphonate (sodium salt).

EXAMPLE 23 This Example illustrates the ixodicidal activity of the derivatives of the invention against cattle ticks (Boophilus microplus).

A suspension of each of the products was prepared by ball-milling 10 parts of the product with 985 parts of water and 5 parts of "Teric" N9 ("Teric" is a Registered Trade Mark and "Teric" N9 is a non-ionic surfactant obtained by condensing nonylphenol with ethylene oxide in a molar ratio of 1:9) to give a composition containing 1.0% active ingredient. A portion of each of the above suspensions was then diluted with water to give compositions containing 0.1 % and 0.01% active ingredient.

The efficacy of each of the products against engorged adult female ticks of the "Yeerongpilly" strain was tested by applying a microdrop of the appropriate concentration suspension to each of about twenty of the ticks. After 14 days the mortality count of the adult ticks was assessed by counting the eggs laid by them and the percentage of those eggs which had hatched. The results are given in Table II.

The efficacy of each of the products against larval ticks of the "Yeerongpilly" strain was tested as follows: A sheet of filter paper was soaked in the appropriate concentration suspension and then allowed to dry. The treated paper was converted to the form of an envelope and approximately 100 larval ticks of the "Yeerongpilly" strain were enclosed therein. A mortality count was done on the larval ticks 48 hours after they had been placed in the envelope and the kill rated on a 0-5 scale wherein 0 represents 0-20% kill 1 represents 20-50% kill 2 represents 50-80% kill 3 represents 80-95% kill 4 represents 95-99% kill 5 represents 100% kill The results are given in Table II.

In a further test an emulsion of each of the products was prepared by mixing 25 parts of the compound with 75 parts of cyclohexanone and 25 parts "Teric" N9 and diluting the mixture with water to provide 10,000 parts by volume of an emulsion. Each of the emulsions so obtained was sprayed, to drip point, on to calves heavily infested with various stages of the resistant "Biarra" strain of cattle tick. The efficacy of each of the products was assessed as follows: (i) All adult female ticks which were fully engorged at the time of spraying were collected soon after spraying the calves. They were then placed in a Petri dish in an incubator for assessment of mortality based on capacity to lay eggs, and if eggs were laid, the viability of the eggs as shown by hatch of viable larvae.Engorged adults, if any, were also collected at 24 hours and 48 hours after spraying and the same assessment of mortality was made. This assessment is referred to as "Mortality-Engorged Adults" and the results are given in Table Ill.

(ii) At daily intervals predetermined sampling areas on each calf were inspected for the effect of the active ingredient on the immature adults and nymphs. This assessment was rated on the 0-5 scale defined in Example 23 and is referred to as "Mortality-Immature Adults" and "Mortality-Nymphs". The results are given in Table III.

The symbol "-" is used to indicate that no engorged adults were present.

In these tests permethrin (3-phenoxybenzyl ( + )-cis/trans-3(2,2-dichlorovinyl)-2,2-dimethylcy- clopropane carboxylate] was used as a standard.

TABLE II IN VITRO IXODICIDAL ACTIVITY AGAINST ADULTS AND LARVAE

% MORTALITY OF ADULTS KILL RATING AGAINST LARVAE PRODUCT 1% a.i. 0.1% a.i. 1% a.i. 0.1% a.i. 0.01% a.i.

3 100 10 5 5 0 4 90 70 5 5 0 5 60 0 5 5 0 6 30 0 5 4 0 7 100 10 5 5 0 9 30 10 2 0 0 14 90 30 5 5 0 17 60 80 5 4 4 20 100 30 4 2 0 21 10 20 5 4 0 24 0 10 5 4 0 27 100 70 4 2 0 37 100 60 5 1 0 41 60 10 5 4 0 42 100 0 5 2 0 43 100 0 5 3 0 TABLE II CONTINUED...

5 MORTALITY OF ADULTS KILL RATING AGAINST LARVAE PRODUCT 1% a.i. 0.1% a.i. 1% a.i. 0.1% a.i. 0.01% a.i.

51 50 0 5 5 0 52 100 90 4 3 0 54 100 100 5 4 0 57 90 30 5 4 0 58 100 30 5 1 0 59 90 0 5 0 0 60 100 50 5 4 0 52 10 0 5 4 0 63 90 40 5 5 0 64 70 0 4 0 0 TABLE III IN VIVO IXODICIDAL ACTIVITY AGAINST ENGORGED ADULTS, IMMATURE ADULTS AND NYMPHS

MORTALITY ENGORGED ADULTS IMMATURE NYMPHS COMPOUND % ACTIVE (% ; 24 hr/24 hr/ ADULTS NO INGREDIENT 48 hr) 3 0.01 -/45/30 3 2 5 0.25 -/75/- 5 3 6 0.25 -/75/50 3 0 9 0.25 100/-/- 5 5 9 0.10 -/100/- 5 3 9 0.05 -/50/50 5 3 17 0.1 100/-/- 5 5 17 0.05 100/100/- 5 5 17 0.025 100/-/- 5 4 17 0.125 40/-/- 5 3 20 0.25 -/100/- 5 5 51 0.25 21/14/17 4 2 52 0.25 -/-/- 5 4 52 0.125 -/-/- 5 4-5 54 0.25 100/100/- 5 5 TABLE III CONTINUED...

MORTALITY ENGORGED ADULTS IMMATURE NYMPHS COMPOUND % ACTIVE (% ; 24 hr/24 hr/ ADULTS NO INGREDIENT 48 hr) 54 0.1 70/-/- 5 3-4 54 0.05 70/-/- 5 2 57 0.25 -/-/- 5 2 58 0.25 100/100/- 5 4-5 EXAMPLE 24 The compounds and compositions of the invention were tested against a variety of foliar fungal disease of plants. The technique employed is to spray the foliage of the plants to maximum retention with a solution or suspension of the test compound and also to apply the same to the roots of the plant via the soil to a final concentration equivalent, approximately, to 40 ppm of the compound in dry soil.Spray formulations on to cereals contain 0. 1% of a surface-active agent.

All solutions or suspension for spraying and application to the soil contained 100 parts per million (ppm) of the test compound, and the plants were grown in potting compost in pots of 4 cm diameter.

The plants were infected with the disease it was desired to control before or after application of the chemical and after a period of days, depending upon the particular disease, (see Table IV) the extent of the disease was visually assessed.

The results are given in Table V below, in the form of a grading as follows: Grading Percentage Amount of Disease 0 61 to 100 1 26 to 60 2 6 to 25 3 0 to 5 4 0 In Table IV below, the disease is given in the first column, whilst in the second column is given the time which elapsed between infecting the plants and assessing the amount of disease.

The third column assigns to each disease a code letter, these code letters being used in Table V to identify the diseases.

TABLE IV

DISEASE AND PLANT TIME INTERVAL DISEASE CODE LETTER (DAYS) (TABLE NO V) (1) Puccinia 10 A recondita (wheat) (2) Phytophthora 3 B infestans (tomato) (3) Plasmopara 7 C viticola (vine) (4) Piricularia 7 D oryzae (rice) (5) Botrytis 3 E cinerea (tomato) (6) Erysiphe 7 F graminis (barley) (7) Cercospora G arachidicola (peanut) TABLE V

COMPOUND A B C D E F G NUMBER 1 4 4 3 4 0 4 - 2 2 4 0 4 2 3 - 3 3 3 0 0 2 2 3 4 2 4 0 2 0 l 0 5 - 3 2 3 2 - 6 4 4 1 3 0 3 - 7 4 3 1 3 0 4- 8 0 4 0 2 1 0- 9 3 4 0 4 0 3- 10 2 4 - 2 1 3 0 11 3 4 - 4 2 3 1 12 2 4 - 2 2 3 0 13 3 4 3 4 0 3 3 14 3 4 3 0 0 2 1 15 2 4 3 3 3 0 1 16 3 3 0 4 0 2 1 17 1 3 0 3 4 3 3 18 4 4 0 4 1 4 4 19 3 4 0 3 2 3 1 20 2 4 0 4 3 4 4 21 4 4 1 4 3 4 3 22 3 4 3 3 0 4 0 23 3 4 0 3 2 3 0 24 4 3 0 3 3 3 1 25 4 3 0 3 3 4 0 26 4 4 1 3 2 1 4 27 4 4 0 3 0 4 3 28 1 4 0 2 1 2 1 29 0 4 0 2 0 2 0 30 1 4 0 2 1 1 0 31 3 2 0 2 1 2 0 TABLE V CONTINUED...

COMPOUND NUMBER A B C D E . F G 32 3 - - 3 3 3 0 33 3 - 0 3 3 2 0 34 2 - - 3 3 3 1 35 3 4 0 0 1 3 36 2 3 0 2 1 3 37 3 - 3 0 2 3 - 38 3 - 3 0 3 3 39 3 4 3 3 1 4 40 3 4 4 4 2 4 41 2 2 0 1 3 0 0 42 4 2 - 3 3 0 0 43 0 1 0 1 3 0 0 44 0 4 0 1 1 3 0 45 0 3 0 0 2 2 0 46 1 4 0 2 0 2 0 47 1 4 0 1 2 0 0 48 2 3 0 2 - 3 0 49 2 3 0 3 - 4 1 50 1 - - 2 2 3 3 51 0 2 0 3 1 4 52 0 3 0 0 0 4 53 3 - 0 3 3 3 0 54 3 3 - 2 0 2 - 55 4 2 - 3 1 3 56 1 3 0 0 2 4 57 1 4 1 3 0 3 - 58 3 4 0 3 1 4 - 59 3 4 2 3 2 3 - 60 4 4 4 4 1 4 - 61 3 4 1 3 2 3 - 62 1 3 4 0 3 0 -

TABLE V CONTINUED...

COMPOUND A B C D E F G NUMBER 63 3 4 3 3 - 4 64 0 2 4 3 - 3 0 In the preceding Table V, the symbol "-" indicates that no test was carried out.

EXAMPLE 25 The invention compounds were tested against the various orders (column 1) and genuses (column 2) in the Table VI below, the types of activity being tested for being also set out (column 3).

TABLE VI

ORDER GENUS TYPE OF ACTIVITY Acarina Tetranychus cinnabarinus Contact/systemic ovicide Hemiptera Aphis fabae Contact, residual systemic, Megoura viciae stomach Trialeurodes vaporariorum Contact and multing disruption on scale Nilaparvata lugens Residual, systemic Lygus lineolarus Lepidoptera Plutella maculipennis Residual, stomach, systemic, anti-feedant, delayed toxicity, moulting disruption Coleoptera Phaedon cochleariae Residual, stomach, moulting disruption, delayed toxicity The results of the tests are set out in Table VII below and the key to the abbreviations heading the columns to this Table are as follows: KEY SCREEN ACTIVITY Al Contact and possible translaminar or systemic activity on Aphis fabae A2 Residual and possible translaminar or systemic activity on Megoura viciae W Contact and possible translaminar or systemic activity on Trialeurodes vaporariorum P Residual and possible translaminar or systemic activity on Nilaparvata lugens PIS Systemic activity on Plutella maculipennis PhS Systemic activity on Phaedon cochleariae M Ad Contact, and possible translaminar or systemic activity on Tetranychus cinnabarinus M Egg Contact ovicidal activity on Tetranychus cinnabarinus 0 represents 0-29% kill 1 represents 30-49% kill 2 represents 50-89% kill 3 represents 90-100% kill A represents anti-feeding above 49% The test procedures were as follows: APHID ACTIVITY Aphis fabae (Al) and Megoura viciae (A2) 1. Contact Test 3" tall broad bean plants in 4" pots are infested with Aphis fabae four days before treatment.

These plants are sprayed at 1000 ppm and soil drenched to give a concentration of chemical in the soil of 60 ppm. When the plants have dried the soil is covered with a 9" square slotted plastic plaque and a 240 mm slotted filter paper. An 8" diameter plastic ring 1+" high, coated with "Fluon" is placed on the plaque encircling the plant to prevent the aphids from escaping.

The number of dead insects are assessed after 2 hours.

2. Residual Test The plants are then infested with Megoura viciae, and mortality assessments of both species are made 2, 4, 24, 30 and 48 hours after spraying. Any plant whose treatment gives 100% kill of Megoura has its filter paper brushed free of dead aphids and is reinfested. Phytotoxic effects on the broad bean are assessed after 10 days.

WHITEFLY ACTIVITY Trialeurodes vaporariorum (W) Contact Test French bean plants in 3" pots at the primary leaf stage are used as host plants. The two primary leaves are cut into 1 i" squares and placed in cages with adults for egg lay for 48 hours. When the scales are only 1 2-1 4 days old these are sprayed with chemical at 1000 ppm and kept for 1 week in a controlled temperature room at 22"C when assessments of scale mortality are made.

PLANTHOPPERS Nilaparvata lugens (P) Five rice plants-variety TNI are grown in 5.5 cm diameter Mono H75 containers. When these are 3-5 cm high they are sprayed with chemical at 1000 ppm on the turntable which deposits 0.96 X 10-5 mg per mm2 on the rice. In addition 5 ml of 1000 ppm solution is added to 100 g of the soil surrounding the rice to give a concentration of 50 ppm in the soil. The plants are left to dry and then silver sand is placed on the soil around the rice, which makes counting of the dead planthoppers easier. Ten adult planthoppers are added to the rice and these are then kept at 25"C under fluorescent lights. The percentage mortality is assessed three days later.

LEPIDOPTERAN ACTIVITY Plutella maculipennis (PIS) Systemic Test A cabbage plant growing in a 1+" diameter pot is left in a plastic dish containing 10 ml of a 250 ppm solution. After 3 days a leaf is detached and placed in a 50 mm petri dish with five 4th instar larvae. Mortality, anti-feeding effects and phytotoxicity are assessed after a further 24 hours.

COLEOPTERAN ACTIVITY Phaedon cochleariae (PhS) Systemic Test A 12" diameter pot containing a mustard plant approximately 100 mm tall is left in a plastic dish containing 10 ml of a 250 ppm solution. After 3 days a leaf is cut and placed in a 50 mm petri dish with five 4th instar larvae. Toxicity, anti-feeding effects and phytotoxicity are assessed after a further 24 hours.

MITE ACTIVITY Tetranych us cinnabarinus Contact (M Ad) and Ovicide (M Egg) Test 3" pots containing French bean plants at the primary leaf stage are used. The two primary leaves are cut into 1-" squares using double scissors, and are infested with adults 24 hours before treatment. Immediately prior to spraying the adults are blown off one leaf with a jet of air, leaving only the eggs. These plants are sprayed at 1000 ppm and the soil drenched to give a concentration of chemical in the soil of 40 ppm. When dry the leaf which is only infested with eggs is detached with a razor blade and placed in a rack in a tray of water to keep it turgid and isolated. The leaf infested with adults is left on the plant, and a 1 50 mm square plastic plaque is placed over the soil to catch any adults which die and drop off.The plants are left in dishes of water and an assessment of adult mortality is made after 3 days and ovicidal activity and phytotoxicity are assessed after 6 days.

TABLE VII

COMPOUND ACTIVITY NUMBER A1 A2 W P PIS PhS M Ad M Egg 1 2 3 N N A A 3 3 2 3 3 N N A 0 2 0 3 0 O N N A O 0 0 4 3 3 N N O 0 3 3 5 3 3 N N A O 0 2 6 O O O N O 0 0 0 7 2 3 N N N N O 0 8 O 0 0 O N O 0 0 0 9 0 O N N O 0 0 0 10 3 3 N N O 0 3 0 11 3 3 N N O 0 3 1 12 1 O N N O 0 3 1 13 3 3 N N A A 3 3 14 3 3 N N O O O 3 15 3 2 N N A A O O 16 3 0 N N O O O O 17 3 O O N N O 0 3 0 18 0 O O N O A O 0 19 O O O N A A O O 20 3 3 O N O 0 2 3 21 3 3 N N O 0 3 3 22 3 3 2 N b 0 3 3 23 3 3 O N A A 3 3 24 0 0 O N O 0 0 0 25 0 2 O N O 0 0 0 26 0 0 O N 0 2 3 0 27 3 3 O N A A 3 3 28 O O O N O 0 0 0 29 0 O O N O 0 0 3 30 0 O O N O 0 0 0 TABLE VII CONTINUED...

COMPOUND ACTIVITY NUMBER Al A2 W ~ P1S PhS M Ad M Egg 31 O O O N O 0 0 0 32 2 2 2 N 0 0 2 3 33 2 3 O N O 0 2 3 34 1 3 N N O A 3 3 35 0 O 2 3 0 0 0 0 36 2 2 0 2 0 0 3 N 37 2 0 N N O N N N 38 1 0 1 2 0 0 1 1 In the foregoing Table VII the letter "N" signifies that no test was conducted and the letter "A" signifies that the test compound produced an anti-feedant effect, that is the insects were put off eating the food, vegetation or plants treated with the test chemical.

Claims

1. Thienopyrimidine and quinazoline derivatives having the general formulae:

wherein R is a straight or branched chain alkyl group optionally substituted with a hydroxy group; Q is hydrogen, phenyl, cycloalkyl or a straight or branched chain alkyl group optionally substituted with one or more halogen atoms, or with an alkoxy- or alkoxyalkoxy-group; X is 0, S or SO,; the number of carbon atoms in R and Q combined being from 5 to 1 8 when R is alkyl and from 3 to 18 when R is hydroxyalkyl ; and optical isomers and salts thereof.

2. Thienopyrimidine derivatives as claimed in Claim 1 having the general formula :

3. Thienopyrimidines as claimed in Claim 2 having the general formula:

wherein R is a straight or branched chain alkyl group; 0 is hydrogen; X is 0; the number of carbon atoms in R being from 5 to 8; and optical isomers and salts thereof.

4. Thienopyrimidines as claimed in Claim 1 having the general formula:

wherein R is a straight or branched chain alkyl group; Q is a straight or branched chain alkyl group optionally halo-substituted; X is 0, the number of carbon atoms in R being from 4 to 7 and Q from 2 to 3; and optical isomers and salts thereof.

5. Thienopyrimidines as claimed in Claim 1 having the general formula:

wherein R is a straight or branched chain alkyl group; Q is a straight or branched chain alkyl group optionally substituted with one or more halogen atoms, or with an alkoxy or an alkoxyalkoxy group; X is O or S; the number of carbon atoms in R being from 3 to 5 and in Q from 2 to 9; and optical isomers and salts thereof.

6. The specific compounds nos 9, 17, 52, 54, 59 and 60 of Table I hereinbefore set forth.

7. A process for preparing the compounds claimed in Claim 1 which comprises either: (i) treating 4-chlorothieno[2,3-d]pyrimidine or 4-chloroquinazoline with an appropriate amine or (ii) treating a 4-alkylamino-thieno[2,3-d]pyrimidine or a corresponding quinazoline, substituted in the alkyl function with a hydroxyl group, with an alkylating agent such as an alkyl bromide, alkyl iodide or dialkyl sulphate.

8. Plant anti-fungal, anti-viral, anti-bacterial, insecticidal, acaricidal and tickicidal compositions comprising as an active ingredient a thienopyrimidine or quinazoline derivative, or an optical isomer of a salt thereof, as defined in any of claims 1 ta 6; together with a carrier for the active ingredient; and optionally, a surface-active agent.

9. A process for combating fungal, viral and bacterial diseases of plants and insect and acarina pests which comprises applying to plants or animals, or to the locus of plants or animals, an anti-fungal, anti-viral, anti-bacterial, insecticidal or acaricidal amount of a thienopyrimidine or quinazoline as defined in any of claims 1 to 6 or a composition as defined in Claim 8.

10. A process for regulating the growth of plants which comprises applying to plants, or to the locus of plants, a thienopyrimidine or quinazoline derivative as defined in any of claims 1 to 6 or a composition as defined in Claim 8.

11. A process for the control or eradication of ticks comprising applying to a media infested with ticks an effective amount of a thienopyrimidine or quinazoline derivative as defined in any of Claims 1 to 6 or a composition as defined in Claim 8.

1 2. A process for the control or eradication of cattle tick (Boophilus microplus) which process comprises applying to said cattle tick, or media infested with said cattle tick, an effective amount of a thienopyrimidine derivative as defined in any of Claims 1 to 6 or a composition as defined in Claim 8.

1 3. A process for the treatment of cattle which comprises treating cattle infested with, or liable to be infested with, cattle tick (Boophilus microplus) with a tickicidally effective amount of a thienopyrimidine or quinazoline derivative as defined in any of Claims 1 to 6 or a composition as defined in Claim 8.