GB2135887A - 4-Alkylamino-quinazolines used as insecticides - Google Patents

Abstract

The invention provides novel 4-(RNH)-quinazolines,wherein R is 2-decyl or 2-undecyl, a process for the preparation of these compounds by reacting the corresponding 4-mols-compounds with an amine RNH2, and their pesticidal use. Another object of the invention is the insecticidal use of 4-n-decylamino- and 4-n-nonylamino-quinazoline.

Description

SPECIFICATION novel quinazolines The present invention relates to novel 4-alkylamino-quinazoline compounds.

4-Alkylamino-quinazolines and their acaricidal use are known i.a. from the USP 3,541,094. The tickicidal use of compounds of this structure class is known from the USP 4,331,667.

It has now been found, that compounds of formula I

wherein R is 2-decyl or 2-undecyl, have very valuable pesticidal properties.

The compounds of formula I are novel; they have hitherto not been specifically disclosed in any publication.

The compound of formula I in which R is 2-decyl [i.e. CH(CH3)-(CH2)7CH3], is hereinafter designated Compound A, the compound of formula I in which R is 2-undecyl (i.e. CH(CH3)-(CH2)8-CH3J is hereinafter designated Compound B.

The present invention provides a process of preparing compounds of formula I which comprises reacting a compound of formula II

therein Xis halogen, with an amine of formula III H2N - R III wherein R is as defined above.

X is preferably selected from CI and Br and is particularly CI.

The process of the invention can be effected in a manner knownperseforthe preparation of 4-alkylamino-quinazoline compounds. The reaction is conveniently effected in the presence of an acid binding agent such as Na2CO3.

The compounds of formula I may be recovered from the reaction mixture in which it is formed by working up according to established procedures. Acid addition salts of compounds of formula I may be converted to the free base form in conventional manner and vice versa.

The compounds of formula II and III are known or may be prepared analogous to known processes resp. to the examples disclosed herein.

The compounds of formula I have surprisingly high tickicidal activity, particularly against strains resistant against tickicidal phosporic acid esters, such as the Mt Alford strain of the cattle tick Boophilus microplus.

The favourable tickicidal activity of the compounds of the invention is iilustrated in Table 1, in which Compound C is 4-(n-CgH19NH) -quinazoline and Compound D is 4(n-C10H21NH)-quinazoline.

TABLE I Effect against the cattle tick, Boophilus microplus Mt Alford, op-resistant strain ppm a.i.

Compound A 2000 100 500 100 125 0 B 2000 100 500 100 125 11 C 2000 11 500 2 125 0 D 2000 78 500 0 125 0 %E = inhibition of reproduction-capacity in % Field test results indicate also a very favourable acaricidal activity of the compounds of formula Representative acaricidal field test results are set out in the following table: TABLE II Acaricidal activity on apple trees (Golden delicious) against the European red mite, Panonychus ulmi, 8 days after application (spray volume 1200 WIha). Effective in % (O/oEl according to the formula of Henderson & BR< Tilton.

Rate in %a.i.

Compound A 0.100 100 0.050 100 0.025 97 B 0.100 100 0.050 100 0.025 96 C 0.100 98 0.050 95 0.025 91 D 0.100 91 0.050 97 0.025 82 It has further surprisingly been found, that various 4-alkylamino quinazolines have also insecticidal, including insecticidal/ovicidal activity. Particularly the compounds of formula IV

wherein R1 is n-nonyl, n-decyl, 2-decyl or 2-undecyl, hereinafter designated compounds of the invention, possess an interesting spectrum of activity, in that they, in addition to their valuable acaricidal activity have an interesting insecticidal activity. The compounds of the invention may exist in free base form or in the form of acid addition salts with mineral or organic acids (e.g. HCI, acetic acid, methane sulphonic acid), they are preferably used in free base form.

The insecticidal activity of the compounds of the invention is indicated by laboratory tests with test concentrations of 20 to 500 ppm against Phaedon cochleariae and of 60 to 1000 ppm against aphids such as Myzus persicae and Aphis fabae. The activity of the compounds of the invention against sucking insects is confirmed by field tests against the pear psylla, Psylla pyri, with test concentrations of 0.025% to 0.1% (spray volume:1200/ha).

Representative test results of the latter field tests are set out in the following table: TABLE Ill Insecticidal activity on pear trees (Wllllams), against thepearpsylla, Psyllapyri, 3 days after application spray volume: 1200l/hat.

Effectiveness in % {%E) according to the formula of Abbott.

Rate in %a.i.

Compound A 0.100 93 0.050 96 0.025 93 B 0.100 98 0.050 93 0.025 88 C 0.100 90 0.050 87 0.025 85 D 0.100 97 0.050 86 0.025 86 Laboratory tests with the 4-alkylamino-quinazolines, particularly with the compounds of the invention, indicate also an interesting insecticidal activity against the eggs of i.a. Spodoptera littoralis, Spodoptera exigua, Anagasta kuehniella, Diabrotica balteata, Epilachna varivestis and Phaedon cochleariae. An indication of the relative order of ovicidal activity is given by the following table.

TABLE IV Ovicidal activity against insect eggs Dosage inducing 95% mortality (LC 95) { > g a. i. 1cm2) Anagasta Spodoptera Phaedon kuehniella littoralis cochleariae Compound A 2.2 1.4 1.7 B 5.9 2.9 1.5 C 1.2 1.9 0.2 D 1.8 5.3 0.6 Chlordimeform 2.7 0.2 26.8 Amitraz 81.9 3.6 24.9 Good ovicidal activity of the compounds of the invention was also found in field trials against the eggs of the grape moth, Lobesia botrana.

TABLE V Ovicidalactivityagainst the eggs of the grape moth, Lobesia botrana (third generation), 33 days after application (spray volume: 180 tTha).

Effectiveness in % (%E) according to the formula of Abbott Rate in %a.i.

Compound A 0.20 85 0.10 67 0.05 63 B 0.20 75 0.10 59 0.05 34 C 0.20 87 0.10 70 0.05 53 D 0.20 52 0.10 52 0.05 37 Amitraz 0.20 26 0.10 46 0.05 35 The spectrum of activity of the compounds of formula I against plant pests is similar to that of Amitraz; their order of activity is in general higher than that of Amitraz. The compounds of the invention are relatively non-toxic and are well tolerated under greenhouse and field conditions by crops such as snap beans, tomatoes, grapes, corn, fruit trees, cotton, peanuts, cole crops and lettuce.

In view of their favourable acaricidal (including tickicidal) and insecticidal (including insecticidal/ovicidal) activity the compounds of formula I are useful in combatting pests such as ectoparasites in animals e.g.

animal livestock (such as cattle and sheep) and phytophagous mites and insects in crops Accordingly, the invention provides a method of combatting pests, which comprises applying to the locus thereof a pesticidally effective amount of a compound of formula I in free base form or in pesticidally acceptable acid addition salt form.

One aspect of this method is a method of combatting ectoparasites in animal livestock which comprises topically applying to the animal an ectoparasitically effective amount of a compound of formula I.

The compounds of formula I are applied to the ectoparasites orto their locus in free base form or in agriculturally acceptable acid addition salt form e.g. as hydrochloride or acetate, by topical treatment of the animals, e.g. by dusting, by dipping or by spray treatments with dilute aqueous form. The compounds of formula I are preferably used in free base form. The degree of dilution may vary within relatively wide limits.

A suitable concentration of the application form is in the range of 0.01 to 5.0%, particularly of 0.02 to 1.1%, by weight of the active agente.g.350g/1000t dip liquid or 2 g resp. 5 g/10g spray liquid. The treatment is preferably repeated at intervals of between 7 to 21 days.

For ectoparasiticidal use, the compounds of formula I are conveniently formulated as a dust, dust concentrate, wettable powder, emulsifiable concentrate or as a solution, with conventional solid or liquid adjuvants, particularly as liquid concentrates, especially as liquid concentrates containing 3.0 to 50% by weight e.g. 20% or 35% by weight of a compound of formula I, such concentrates being diluted with water before use. Such liquid concentrate preferably includes an emulsifying agent such as a polyglycolether derived from a high molecular weight alcohol, mercaptan or alkyl phenol with an alkylene oxide as well as a diluent such as a liquid aromatic hydrocarbon or mineral oil.

The ectoparasites against which the compounds of formula I are effective include ticks and blowflies. Ticks against which the use of the compounds of formula I is indicated include those of the family Ixodidae e.g. the cattle ticks such as Boophilus decoloratus and Boophilus annulatus, Rhipicephalus spp such as Rhipicephalus sanguineus, Rhipicephalus appendiculatus, Rhipicephalus pulchellus and Rhipicephalus evertsi, Hyalomma spp such as Hyalomma trucatum, Hyalomma rufipes, Hyalomma detritum, Hyalomma marginatum, Hyalomma dromedarii and Hyalomma anatolicum excavatum, Amblyomma spp such as Amblyomma variegatum, Amblyomma hebraeum, Amblyomma pomposum, Amblyomma americanum, Amblyomma cayennense, Amblyomma maculatum, Amblyomma gemma and Amblyomma lepidum; those of the family Argasidae, e.g. Otobius spp such as Otobius megnini and Ornithodoros spp such as Ornithodoros savignyi, Ornithodoros lahorensis and Ornithodorostholozani; those of the family Psoroptidae e.g. Psoroptes ovis and Psoroptes equi; and those of the family Sarcoptidae e.g. Sarcoptes bovis or Sarcoptes scabiei. Blowflies against which the use of the compounds of formula I is indicated include the Lucilia spp, such as Lucilia cuprina and Lucillia sericata, in sheep.

The excellent acaricidal activity of compounds of formula i against phytophagous mites in combination with their insecticidal activity is an important advantage of these compounds over many pyrethroids which, whilst having insecticidal activity tend rather to increase the mite population in plants.

Another aspect of the method of combatting pests, is a method of combatting phytophagous mites and/or insects in crops which comprises applying to the crop locus a miticidally and/or insecticidally effective amount of a compound of formula i. Moreover, the present invention provides the insecticidal use of the compounds of the invention in crops, which comprises applying to the crop locus an insecticidally effective amount of the compounds of the invention.

For miticidal and/or insecticidal use of a compound of formula I resp. the insecticidal use of the compounds of the invention, the amount to be applied to attain the desired effect will vary depending on the particular crop and other standard variables such as the compound employed, mode of application, conditions of treatment and the like.

The appropriate application rates can be determined by routine procedure by those skilled in the art, or by comparing the activity of the compounds of the invention with standards for which the application rate is known, e.g. in greenhouse tests. However, in general, satisfactory results are usually obtained when the compound is applied in concentrations in the range of from about 0.01% to 1% preferably from about 0.02% to 0.2% by weight of the active agent, the application being repeated as necessary. For crop protection the spray volume will in general vary between 50-1000t/ha of crop. The concentration of the spray liquid will vary depending on the mode of application and the spray volume.In general the relation between spray concentration and spray volume will be selected such, that the active agent is applied in an amount of 100-1000 g, more preferably of 200-500 g per hectare of crop locus.

Crops in which the miticidal use of the compounds of formula I is indicated, are fruit crops (e.g. stone fruit crops such as almond, apricot, peach, plum and prune crops; citrus fruit crops such as grapefruit, lemon, lime, mandarin, orange and tangerine crops; pome crops such as apple, pear and quince crops; and vineyards), cotton and vegetables (e.g. tomatoes, egg-plants, peas, beans, cucumbers).

Mites against which the compounds of formula I are indicated to be particularly effective include by way of example: TETRANYCHUS URTICAE**, Two-spotted spider mite, T. PACIFICUS, Pacific spider mite, T. ATLANTICUS, T. VIENNENSIS, EOTETRANYCHUS CARPINI, PANONYCHUS ULMI**, European red mite, P. CITRI, Citrus red Mite, PHYLLOCOPTRUTA OLEIVORA, Citrus rust mite including strains resistant to phosphoric esters.

Crops in which the insecticidal use of the compounds of formula I, resp. of the Compounds C and D is indicated are: Cotton Pomefruits Corn Stone fruits Soybean Grapes Potatoes Citrus Tobacco Vegetables, e.g. Cole crops Rice Leguminous crops Cucumber.

Insect pest against which the compounds of the invention are indicated to be particularly effective include by way of example: in cotton, corn and vegetables: Lepidoptera, particularly SPODOPTERA spp (especially eggs) such as: S. LITTORALIS, S. LITURA, S. FRUGIPERDA, S. EXIGUA, HELIOTHIS spp. (especially eggs) such as: H. ARMIGERA, H.ZEA, H. VIRESCENS DIABROTICA spp. (Corn rootworms), Coleoptera, (especially eggs) such as: D. UNDECIMPUNCTATA; in potatoes: LEPTINOTARSA DECEMLINEATA, Coleoptera, (especially eggs and young larvae); in pome fruits: PSYLLA PYRI.Homoptera, (especially young nymphs), LASPEYRESIA POMONELLA, Lepidoptera, (especially eggs); in grapes: Lepidoptera like LOBESIA POTRANA (especially eggs) and EUPOECILIA AMBIGUELLA (especially eggs); in cole crops.' Lepidoptera like PIERIS spp. (especially eggs).

PLUTELLA XYLOSTELLA (especially eggs), Coleoptera like PHAEDON COCHLEARIAE (especially eggs).

in rice: Lepidoptera like CNAPHALOCROCIS MEDINALIS, rice leaf-roller (especially larvae); Homoptera like NEPHOTETTIX CINCTICEPS, green rice leaf-roller (especially nymphs and adults); and NILAPARVATA LUGENS, brown rice plant hopper (especially nymphs and adults).

The compounds of the invention may be and preferably are employed as pesticidal compositions (more particularly tickicidal, miticidal and insecticidal compositions) in association with agriculturally acceptable diluent(s). Suitable formulations contain 0.01% to 99% by weight of a compound of the invention, from 0 to 30% agriculturally acceptable surfactant and 1 to 99.99% diluent(s). Higher ratios of surfactant to active ingedient are sometimes desirable and are achieved by incorporation into the formulation or by tank mixing.

Application forms of composition generally contain between 0.01 and 25% by weight of a compound of the invention. Lower or higher levels of active ingredient can, of course, be present depending on the intended use and the physical properties of the compound. Concentrate forms of composition intended to be diluted before use generally contain between 2 and 90%, preferably between 10 and 80% by weight of a compound of the invention.

Useful formulations of the compounds of the invention include dusts, granules, pellets, suspension concentrates, wettable powders, emulsifiable concentrates and the like. They are obtained by conventional manner, e.g. by mixing the compounds of the invention with the diluent(s). More specifically liquid compositions are obtained by mixing the ingredients, fine solid compositions by blending and, usually grinding, suspensions by wet milling and granules and pellets by impregnating or coating (performed) granular carriers with the active ingredient or by agglomeration techniques.

Alternatively, the compounds of the invention e.g. the compounds of formula I may be used in microencapsulated form.

Agriculturally acceptable additives may be employed in the pesticidal compositions e.g. to improve the performance of the active ingredient andlor to reduce foaming, caking and corrosion.

Surfactant as used herein means a agriculturally acceptable material which imparts emulsifiability, spreading, wetting, dispersibility or other surface-modifying properties. Examples of surfactants are sodium lignin sulphonate and lauryl sulphate.

Diluents as used herein means a liquid or solid agriculturally acceptable material used to dilute a concentrated material to a usable or desirable strength. For dusts or granules it can be e.g. talc, kaolin or diatomaceous earth, for liquid concentrate forms, for example a hydrocarbon such as xylene or an alcohol such as isopropanol, and for liquid application forms i.a. water or diesel oil.

The above pesticidal compositions comprising a compound of formula I as active agent also form part of the invention.

The compositions of this invention can also comprise other compounds having biological activity, e.g.

compounds having similar or complementary tickicidal, miticidal or insecticidal activity or compounds having fungicidal or herbicidal activity.

Specific examples of pesticidal (tickicidal/miticidal/insecticidal) compositions will now be described. Example A : Wettable Powder 25 Parts of a compound of formula I, e.g. Compound B hereinafter given, are mixed and milled with 25 parts of synthetic fine silica, 2 parts of sodium lauryl sulphate, 3 parts of sodium ligninsulphonate and 45 parts of finely divided kaolin until the mean particle size is about 5 micron. The resulting wettable powder is diluted with water before use to a spray liquor with the desired concentration.

Example B: Emulsifiable Concentrate 20 Parts of a compound of formula I, e.g. Compound B hereinafter given, 40 parts of xylene, 30 parts of dimethyl formamide and 10 parts of emulsifier (e.g. ATLOX 4851 B a blend of Ca alkylarylsulphonate and a polyethoxylated triglyceride of Atlas Chemie GmbH) are thoroughly mixed until a homogeneous solution is obtained. The resulting emulsifiable concentrate is diluted with water before us Example C: Granules 5 Kg of a compound of formula I, e.g. Compound B hereinafter given, are dissolved in 25t methylene chloride. The solution is then added to 95 kg of granulated attapulgite (mesh size 24/48 mesh/inch) and thoroughly mixed. The solvent is then evaporated off under reduced pressure.

The invention is further illustrated by the following Examples wherein temperatures are in "C, pressures are in Torr and Rf values are on silica gel, so far not otherwise indicated.

FINAL PRODUCTS Example 1: 4-(Decyl-2-amino)-quinazoline To a stirred mixture of 165.5 g 4-chloro-quinazoline and 700 ml water are added portion-wise 64 g soda, and thereafter, in one time, 160 g 2-aminodecane. The reaction temperature rises slightly and the solid flask content becomes weak and unctuous. The reaction mixture is stirred firmly, first one hour without heating and then 3 hours at 80". Thereafter the reaction mixture is cooled to 25 and stirred until the unctuous flask content becomes so solid that it is possible to suck it off. The thus obtained product is thoroughly washed with water and dried under water jet vacuum at 500 to give the relatively pure title product, m.p. 96".

Crystallisation from acetonitrile yield the title product having a m.p. of 1000.

Example 2 : 4-(Undecyl-2-amino)-quinazoline The title compound is obtained analogous to the procedure of Example 1, using 174.5 g 2-aminoundecane instead of 160 g 2-aminodecane; m.p. 102" (from acetonitrile).

INTERMEDIATES Example 3: 2-Aminodecane To a mixture of 1100g methyl-octylketone in 2000 ml ethanol are added 184g liquid ammonia and 125g Raney-Ni. The mixture is hydrogenated in the autoclave at 80" under 100 bar. The hydrogenation is complete after 15 hours. The Raney-Ni is then filtered off, the excessive ammonia evaporated (1 hour reflux), the reaction mixture cooled off, acidified with 1000 ml (10 Mol) conc. HCI and evaporated till dryness under water jet vacuum. The residue is treated with 1000 ml 30% NaOH and 400g ice, the title compound partitioned off from the aqueous phase and distilled b.p.91 -93 120 mm. The thus obtained title compound, comprising about 10% impurities, is used as such in the process of Example 1.

Example 4: 2-Aminoundecane The title compound is obtained analogous to the process of Example 3 by hydrogenation of methly-nonyl-ketone in the presence of liquid ammonia and Raney-Ni. The distillation is effected at 105-107 /18 mm.

Claims (25)

1. A method of combatting insects in a crop locus which comprises, applying to the crop locus insecticidally effective amount of a compound of formula IV

wherein R1 is n-nonyl, n-decyl, 2-decyl or 2-undecyl in free base form or agriculturally acceptable acid addition salt form.

2. The method of Claim 1 wherein R1 is 2-decyl or 2-undecyl.

3. A process for the production of compounds of formula I

wherein R is 2-decly or 2-undecyl in free form or in acid addition salt form, which comprises reacting a compound of formula 11

wherein Xis halogen, with an amine of formula III H2NR Ill wherein R is as defined in this Claim, and recovering the the thus obtained compounds of formula I in free form or in acid addition salt form.

4. Process according to Claim 3 substantially as described herein by way of Example.

5. Product by a process according to Claim 3 or 4.

6. A compound of formula I, stated in Claim 3, in free form or in acid addition salt form.

7. The compound according to Claim 6, wherein R is 2-decyl.

8. The compound according to Claim 6, wherein R is 2-undecyl.

9. A method of combatting pests, which comprises applying to the pest locus a pesticidally effective amount of a compound of formula I, stated in Claim 3, in free base form or agriculturally acceptable acid addition salt form.

10. A method according to Claim 9, wherein the pests are ectoparasites.

11. A method according to Claim 10, wherein the pest locus is an animal.

12. A method according to Claim 11, wherein the pest locus is an animal livestock.

13. A method according to Claim 12, wherein the compound of formula I is applied from a dilute aqueou solution by spraying or dipping the animal.

14. A method according to Claim 13, wherein the active agent is applied as a 0.01 to 5 % by weight aqueous solution.

15. A method according to Claim 13, wherein the active agent is applied as a 0.02 to 0.1% by weight aqueous solution.

16. A method according to Claim 13 for the treatment of cattle or sheep.

17. A method according to Claim 9, wherein the pest locus is a crop locus.

18. A method according to Claim 17, wherein the pests are phytophagous mites.

19. A method according to Claim 17, wherein the pests are phytophagous mites and insects.

20. A method according to Claim 17, wherein the compound of formula I is applied at a rate of 100 to 1000 g per hectare crop locus.

21. A method according to Claim 20, wherein the application rate is from 200 to 500 g of active agent per hectare of crop locus.

22. A pesticidal composition, comprising a compound of formula I, stated in Claim 3, in free form or in agriculturally acceptable acid addition salt form, in association with agriculturally acceptable diluent(s).

23. A composition according to Claim 22 containing 0.01% to 90% by weight of active agent.

24. A composition according to Claim 23 in concentrate form containing 2% to 90% by weight of active agent.

25. A composition according to Claim 23 in application form containing 0.01% to 25% by weight of active agent.