SK166297A3 - Use of oxazolines for combatting ectoparasites - Google Patents

Abstract

The present invention relates to the use of compounds of formula (I) in which B is possibly substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, A is aryl, aryloxy, heteroaryl, heteroaryloxy which may be substituted and may be bonded to the oxazoline ring via a divalent radical Z, R is hydrogen or, together with A and the adjacent C atom, a spirocyclic 3 to 6-member ring which may contain one or more heteroatoms of the O, S, N group and may be condensed on a further ring, where the system may be substituted, for combatting insects and monoxenous ticks on humans and animals.

Description

Technical field

The invention relates to the use of oxazolines for controlling ectoparasites as well as ectoparasiticidal compositions containing oxazolines.

BACKGROUND OF THE INVENTION

Oxazolines, as well as their production and their use as insecticides and acaricides in plant protection, as well as against certain animal insects, are already known. However, nothing has yet been disclosed about their use against ectoparasites and, in particular, against insects and single-host ticks.

SUMMARY OF THE INVENTION

It is an object of the present invention to use oxazolines of the formula I

A

O— ¹ in which

B represents an optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl group,

A represents an aryl group, an aryloxy group or a heteroaryloxy group which are optionally substituted and which are optionally linked via a bivalent radical Z to an oxazoline ring and

R is a hydrogen atom or, together with A and the adjacent carbon atom, a spirocyclic three to six membered ring which may optionally contain one or more heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen;

30841 / H, which is optionally fused to another ring, wherein the system is optionally substituted, for controlling parasitic insects and monostable ticks in humans and animals.

For example, compounds of formula I are the subject of the following patent applications: WO 93/21 165, WO 93/24 470, JP-OS H4 89 484, JP-OS H6 145 155, JP-OS H6 145 169, JP-OS H6 100 546 JP-OS H6 100 560, JP-OS H6 73 030, EP-OS 345 775, EP-OS 432 661, EP-OS 553 623, WO 93/22297 and WO 93/25 079.

Particular consideration is given to preferred groups of compounds as well as the individual compounds and their production method.

Preferred are compounds of formula I wherein the substituents have the following meanings:

An optionally substituted alkyl group alone or as part of a radical in the formulas is a straight or branched alkyl group having 1 to 20 carbon atoms, in particular 1 to 18 carbon atoms. Exemplary and preferred meanings include optionally substituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, neopentyl, undecyl, dodecyl, pentadecyl and octadecyl groups.

An optionally substituted alkenyl group as well as an alkenyl moiety such as an optionally substituted alkenyloxy or alkenylthio group in the general formulas represents a straight or branched alkenyl group having preferably 2 to 6, in particular 2 to 4, carbon atoms. By way of example and preferably, an optionally substituted ethenyl, 1-propenyl, 2-propenyl and 3-butenyl group may be mentioned.

An optionally substituted alkynyl group as well as an alkenyl moiety such as an optionally substituted alkynyloxy or alkynylthio group in the general formulas represents a straight or branched alkynyl group having preferably 2 to 6, in particular 2 to 4, carbon atoms. By way of example and preferably, optionally substituted ethynyl, 1-propynyl, 2-propynyl and 3-butynyl may be mentioned.

Optionally substituted cycloalkyl alone or as part of a radical in the general formulas represents a monocyclic, bicyclic and tricyclic cycloalkyl group having preferably 3 to 10 carbon atoms, in particular 3, 5 or 6 carbon atoms. By way of example and preferably, an optionally substituted cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl group may be mentioned.

An optionally substituted alkoxy alone or as part of a radical in the formulas is a straight or branched alkoxy group having preferably 1 to 6 carbon atoms, in particular 1 to 4 carbon atoms. Exemplary and preferred meanings include optionally substituted methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and tert-butoxy.

An optionally substituted alkylthio group alone or as part of a radical in the formulas is a straight or branched alkylthio group having preferably 1 to 6 carbon atoms, in particular 1 to 4 carbon atoms. Examples of preferred and preferred meanings include optionally substituted methylthio-, ethylthio-, n-propylthio-, isopropylthio-, η-butylthio-, isobutylthio- and tert-butylthio-upin.

Optionally substituted carbalkoxy alone or as part of a radical in the general formulas means a straight or branched carbalkoxy having preferably 2 to 7 carbon atoms, in particular 2 to 5 carbon atoms. Exemplary and preferred meanings include optionally substituted carbomethoxy, carboethoxy, carbo-n-propoxy, carboisopropoxy, carbon-butoxy, carboisobutoxy, and carbo-tert-butoxy.

Haloalkyl alone or as part of a radical in the formulas, such as haloalkoxy or haloalkylthio, means a straight or branched haloalkyl of preferably 1 to 4 carbon atoms, especially 1 or 2 carbon atoms and preferably 1 to 5, especially 1 to 3 carbon atoms with the same or different halogen atoms, preferably halogen, fluorine, chlorine and bromine, in particular fluorine and chlorine. Examples of preferred and preferred meanings are trifluoromethyl, chlorodifluoromethyl, bromomethyl, 2,2,2-trifluoroethyl and pentafluoroethyl.

An optionally substituted aryl group alone or as part of a residue in the general formulas, such as aryloxy, arylthio and arylalkyl, is preferably an optionally substituted phenyl or naphthyl group, in particular phenyl.

An optionally substituted arylalkyl group in the general formulas represents an optionally substituted aryl and / or alkyl portion of an aralkyl group having preferably 6 or 10 carbon atoms in the aryl portion (preferably phenyl or naphthyl, especially phenyl), and preferably 1 to 4 carbon atoms, in particular 1 to 2 carbon atoms in the alkyl moiety, wherein the alkyl moiety may be straight or branched. By way of example and preferably, optionally substituted benzyl and phenylethyl groups may be mentioned.

An optionally substituted heteroaryl group alone or as part of a radical in the general formulas, such as heteroaryloxy, heteroarylthio or heteroarylalkyl, means 5- to 7-membered rings with preferably 1 to 3, in particular 1 or 2, identical or different heteroatoms which conform to the aromatic principle of Helicelic. The heteroatoms include oxygen, sulfur or nitrogen. An optionally substituted thienyl group may be mentioned by way of example and preferably.

The optionally substituted radicals of the formula I can carry one or more, preferably 1 to 3, in particular 1 to 2, identical or different substituents. The substituents include, but are not limited to:

C 1 -C 20 alkyl, especially C 1 -C 18, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, neopentyl, hexydecyl a group, an octadecyl group; (C až-C 14) alkoxy, especially C 1-C 4, such as methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, tert-butyloxy; alkylthio having preferably 1 to 4 carbon atoms, in particular 1 or 2 carbon atoms, such as methylthio, ethylthio, n-propylthio, lopropylthio, n-butylthio, isobutylthio and tert-butylthio; haloalkyl having preferably 1 to 4 carbon atoms, in particular 1 or 2 carbon atoms and preferably 1 to 5 halogen atoms, in particular 1 to 3 halogen atoms, the halogen atoms being the same or different and preferably fluorine, chlorine or bromine, especially fluoro such as difluoromethyl or trifluoromethyl; hydroxy; a halogen atom, preferably fluorine, chlorine and bromine, in particular fluorine and chlorine; cyano; nitro; amino; monoalkylamino and dialkylamino having preferably 1 to 4 carbon atoms, especially 1 to 2 carbon atoms in each alkyl group, such as methylamino, methylethylamino, n-propylamino, isopropylamino and methyl-n-butylamino; acyl radicals such as formyl, alkylcarbonyl, for example acetyl or arylcarbonyl, for example benzoyl; carboxy having preferably 2 to 4 carbon atoms, in particular 2 or 3 carbon atoms, such as carbomethoxy and carboethoxy; (C 1 -C 4) alkylsulphinyl, in particular 1 or 2 carbon atoms, haloalkylsulphinyl (C 1 -C 4), especially (C 1 -C 2) carbon atoms, and C 1 to 5 halogen atoms such as trifluoromethylsulphinyl; a sulfonyl group (-SO ₃ H); alkylsulfonyl having preferably 1 to 4 carbon atoms, in particular 1 or 2 carbon atoms, such as methylsulfonyl and ethylsulfonyl; haloalkyisulfonyl having 1 to 4 carbon atoms, in particular 1 to 2 carbon atoms and 1 to 5 halogen atoms, such as trifluoromethylsulfonyl and perfluoro-t, n, s-butylsulfonyl; an arylsulfonyl group having preferably 6 or 10 carbon atoms, such as a phenylsulfonyl group; an acyl group; aryl; aryloxy; a heteroaryl group; heteroaryloxy, which alone may carry any of the above substituents, as well as a formimino group of the formula -CH = NO-alkyl.

Advantageously, compounds of the formula I can be mentioned in which the substituents have the following meanings:

B represents an alkyl group having 1 to 8 carbon atoms which is optionally one or more times, equally or differently substituted by a halogen atom, a cyano group, an alkoxy group having 1 to 4 carbon atoms, and optionally one to three times as well or a different halogen atom, an alkyl group (C 1 -C 4) -haloalkyl, (C 1 -C 4) -haloalkyl, (C 1 -C 4) -alkoxy, (C 1 -C 4) -haloalkyloxy, (C 1 -C 4) -alkylthio and / or (C 1 -C 4) -haloalkylthio (C 1 -C 4) -alkyl; substituted phenyl, phenoxy, benzyloxy, phenylthio and benzylthio, alkenyl of 2 to 8 carbon atoms, substituted one or more times, as well as different halogen, cycloalkyl of 3 to 8 carbon atoms, optionally one or more times, a differently substituted atom m is halogen, alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, haloalkyl of 1 to 4 carbon atoms or haloalenyl of 2 to 4 carbon atoms, cycloalkenyl of 5 to 7 carbon atoms which is optionally one or more times, equally or differently substituted by halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl, phenyl, optionally one to four times, equally or differently substituted, with the substituent being the atom halogen, (C 1 -C 4) -alkyl, (C 1 -C 4) -alkoxyalkyl, (C 1 -C 4) -haloalkoxy, (C 1 -C 4) -haloalkyl, (C 1 -C 4) -alkoxy is optionally interrupted by another C1 -C4 alkylthio, C1 -C4 alkylthio and C1 -C4 haloalkylthio;

A is optionally one to four times, as well as differently substituted phenyl, benzyl, phenet-1-yl, phenet-2-yl, phenoxymethyl, phenylthiomethyl, phenoxyet-1-yl, phenylthioet-1-yl, phenoxyet-2-yl and styryl phenyl substituents such as halogen, C1-C18alkyl, C1-C8alkoxyalkoxy, C1-C8haloalkoxy, C1-C4haloalkyl , (C 1 -C 18) alkoxy optionally interrupted by an additional 1 to 3 oxygen atoms, (C 1 -C 8) alkylthio, (C 1 -C 8) haloalkylthio,

3.4- difluoromethylenedioxy,

3,4-tetrafluoroethylenedioxy, benzyliminooxymethyl, optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl and / or halogen, cyclohexyl and cyclohexyloxy, in each case optionally substituted with C1-C6 alkyl, (C 1 -C 6) alkoxy, cyclohexyl or phenyl, pyridyloxy substituted, optionally once or twice, as well as different halogen, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl or phenyl, benzyl phenoxy, phenylthio, benzyloxy and benzylthio, in each case optionally substituted one to three times, as well as different alkyl groups having 1 to 12 carbon atoms, halogen atoms, haloalkyl groups having 1 to 4 carbon atoms, alkoxy groups having 1 to 3 carbon atoms 6 carbon C1 -C6 haloalkoxy, C1 -C6 alkoxyalkyl, C1 -C6 alkoxyethylene, C1 -C6 alkylthio and / or C1 -C6 haloalkylthio; atoms and

R is preferably a hydrogen atom.

Particular preference is given to compounds of the formula I in which the substituents have the following meanings:

B represents an alkyl group having 1 to 6 carbon atoms, which is optionally one or more times, equally or differently substituted by a fluorine, chlorine or bromine atom, a cyano group, an alkoxy group having 1 to 2 carbon atoms, and optionally one or two times as well or differently fluoro or chloro, C 1 -C 4 alkyl, C 1 -C 2 haloalkyl, C 1 -C 2 alkoxy, C 1 -C 2 haloalkoxy, C 1 -C 2 alkylthio and / or haloalkylthio 1 to 2 carbon atoms, substituted by phenyl, phenoxy, benzyloxy, phenylthio and benzylthio, alkenyl of 2 to 6 carbon atoms, substituted one or more times, as well as different fluorine and / or bromine atoms, cycloalkyl of 3 to 8 carbon atoms which is optionally one or more times, equally or differently substituted by fluorine or chlorine, alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, haloalkyl of 1 to 2 carbon atoms of fluorine and / or chlorine as halogen atoms, or haloalkenyl having 2 to 4 carbon atoms with fluorine and / or chlorine as halogen atoms, a cycloalkenyl group of 5 to 7 carbon atoms, which may optionally be mono- or poly-substituted, as well as differently or differently by fluorine or chlorine, alkyl of 1 to 4 carbon atoms or haloalkyl a C 1 -C 2 fluorine and / or chlorine halogen atom, a phenyl group, optionally one to four times, equally or differently substituted, with a fluorine, chlorine or bromine atom being a C 1 -C 4 alkyl group C1-C4alkoxy one to six times the same or differently substituted by a fluorine and / or chlorine atom, or an alkyl group having 1 to 2 carbon atoms which is one to five times the same or differently substituted by a fluorine and / or chlorine atom,

A is particularly preferably 1 to 4 times, as well as differently substituted phenyl, benzyl, phenet-1-yl, phenet-2-yl, phenoxymethyl, phenylthiomethyl, phenoxyet-1-yl, phenylthioet-1-yl, phenoxyet-2-yl and styryl, the phenyl substituents being fluorine, chlorine or bromine, alkyl of 1 to 18 carbon atoms, alkoxyalkyl of 1 to 8 carbon atoms in both alkyl and alkoxy, alkoxy of 1 to 8 carbon atoms, 1 to 8 carbon atoms six times, identically or differently by fluorine and / or chlorine, alkyl having 1 to 2 carbon atoms substituted one to five times by identical or different fluorine and / or chlorine, alkoxy having 1 to 18 carbon atoms and - (OC 2 H ₄₎ i A 3-O-C 1 -C 3 -alkyl group, an alkylthio group having 1 to 12 carbon atoms, an alkylthio group having 1 to 8 carbon atoms, one to six times, the same or differently substituted f urine and / or chlorine,

3.4- difluoromethylenedioxy,

3.4- Tetrafluoroethylenedioxy, groups

Z is cyclohexyl and cyclohexyloxy, in each case optionally substituted by alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms; 4 carbon atoms, cyclohexyl or phenyl, pyridyloxy optionally substituted once or twice, as well as different fluorine or chlorine atoms or trifluoromethyl, or phenyl, benzyl, phenoxy, phenylthio, benzyloxy and benzylthio, in each case optionally substituted 1 to 2; three times, same or different alkyl of 1 to 12 carbon atoms, fluorine, chlorine, bromine, trifluoromethyl or alkoxy of 1 to 4 carbon atoms, 1 to 6 times, same or different of fluorine and / or chlorine substituted with 1 to 4 C 1 -C 4 alkoxyalkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 4 alkoxyethyleneoxy, C 1 -C 4 alkylthio and / or one to six times the same or different fluorine and / or chlorine substituted alkylthio with 1 to 4 uh with atomic atoms and

R is particularly preferably a hydrogen atom.

A and R in the formula I together may advantageously form spirocyclic rings, which themselves may again be, for example, substituted by A radicals:

wherein A is as defined above and

R ² represents hydrogen or one of the substituents mentioned for A.

Particularly particularly preferred are compounds of formula I in which residue A is characterized by the following formula, which may be attached to the oxazoline ring either directly or via a bridging member Z:

while

R ¹ is the radicals according to the following Table 1 and (R ² ) m is the radicals listed in the following Table 2.

Table 1

R ¹ R ¹ Cl -OCF ₂ CHFCF ₃ F CH, CH-O-C, H, -C _and Ho-t -CH, CH, -OC ₄ Ho-ii • ΌςΗ ,, - η CH, CH, H OC ₆ "-n C], H, ₃ -n -CH ₂ - o -n Cl -C, _n H, - n -SC ₄ Ho-n -SC ₆ H ,, - n "CqHjq-Π -SCn H ₁₇ -n CF, -SC H, ^ - N -CF, CHF, -SCF. -OC _Ä H ,, - n -SCF, CHF, -0C _R H ₁₇ -n -SCFiCHFCH. -OCl, H, _s -n -CO-CH -ocf ₃ 0 -ocf ₂ chf ₂ C ₄ H 3 -t -och, cf ₃ - -0 ° -OCF, chfch ₃ ~ ° \ Zy ^{c, Hi} ' -CO-C ^ -i ABOUT

Table 1 (continued)

R ¹ R ¹ -O ^ci \ j / - ^c - ^h · ^{5 CI} 7 - = \ ^- O ^- ' _{_} _ <CI - (1½ _t- Cl 2 Cl _ _r ci —0 - ^ - CH-O-O- ^CI about About ^cf > -? -? - ° ^cF = o ^C 3 ^H f ⁿ ch ₃ -O- ^cr ' S ^> = '· about CH 0 ^} - ocf ₄

Table 1 (continued)

R ¹ R ¹ ——OCHF ₂ ^Cl > = \ -ί / *, cr ^_ch '\ 2 ^ ^_ ° ^cf > ch ₃ CH, -about -chhQ - ° -Ο ~ ^{α CH 2} H 2 ^F ~ ^o— C ^ ^ - ^Br "O ^- "' / ^Br - ° -O ~ ^{c, Grn} - ^CH : -O- ^W ' - ⁰ -V ^ ^"CIHR “ ^CH 2 ~ ^ ^Ο 6 ^Η ίΓ ^η - ° 4> ° ο _Λ ”CHj-C jjHjj · n ch ₃ -θ-θ- '»'.

Table 1 (continued)

R ¹ r ' ^Cl > = ”° y ° ^CH3 '' O ' ⁰ · - ° \ 2 ^ ° ^{chf c} > \ _ “° \\ // ^0CH 3 CP ' - -ζ ° - ^ - ^ F OCH, ^'0' ^ d ^{'CH 2} ° ^CIHIE - ° ^CF · - - - - - - - CH 2 F -about- -o · ^ ^ -ocf ₂ chfcf ₃ - ° The -what- Cl O-0-CF Cl n- ch ₃ • ^o O ~ ^cf · ch ₃

Table 1 (continued)

R ¹ R ¹ Cl - ° y 5 ~ ^0CH 'Cl -CH ₂ H ₂ O ₃ c ₄ Ht CH ₃ . - ° / z>' ^OCH 3 CH, à ^J -ο ^ -θ-ορ, Tf ^OCH 2 ^CF I ° ^ CL_ ^"0CH ^ \ _ / - ^CF3 -o2-scf ₂ chf ₂ ^Cl z = \ - ° ^εΗ τζ> ^οε Η ₃ ^N = 1 ° / ^CF 3 Cl - ^with ^ W) - ° The ^S W ' ^C ' ^Cl &lt; - &gt; = - V / ^SCH3 - ^with ^ 0- ^{& 0CH} ťCy- ^cl ' ^s O ^cFi - ^with -O- ° ^cf , Cl? - ° ^ΟΗ 2-4Λ-α H -CO-O-C _d Ho-t -CO-NH-CHO-t CN 5

Table 2

(R ²⁾ _m H _2-CH3 2-Cl 2-OCH ₃ 2-F 2,3-Cl ₂ 3-Cl Wixyy. 2,6-Cl ₂ 3-CH ₃ 3,5-Cl ₂ 3,5- (00¾ 3,5-F ₂ 3-OC ₆ H ₅ 2,5-Cl ₂ 3,5-Cl ,; 2-F . í R ¹ 2,3-F ₂ 3,4- (OCF ₂ O-) 2,5-F, 3,4- (OCF ₂ CF ₂ O) 2,3,5,6-Cl ₄ 2-Cl; 3-CF ₃ 3-CF 2-Cl; 5-CF

By way of example, for the substituents A, the radicals listed in Table 1a below are attached to the oxazoline ring either directly or via a bridging member Z.

Table 1a

Rest A Rest A al --— Heptyl-n a6 _x Nonyl-n -Cl · a2 A7 —— Decyl-n a3 N-octyl a8 -oW a4 -/IN A9 -CKC; a5 -about alO N-dodecyl

Table 1a (continued)

Rest A Rest A all -Pentadecyl n a20 N-heptyl al2 J -O ¹ - a21 ^C '? - (-? - Octyl-n AI3 -Octyl-N a22 ch ₃ -Octyl-n AL4 a23 N-decyl AL5 a24 N-dodecyl AL6 a25 ^C u_ —y-Dodecyl-n ' AL7 about- a26 CL · _ —Y- Decyl-n AL8 N-nonyl a27 ^CH 3 ^O 3 - Octyl-n and? 9 - ^ - n-Nonyl a28 ^CH . Nonyl-n

Table 1a (continued)

Rest A Rest A a29 yl-Decyl-N a39 - C 1 H - Octyl-n a30 N-nonyl a40 —0 - Heptyl-n a31 - ^ - undecyl-n a41 a32 —T ridecyl-n a42 —0-Octyl-n a33 - ^ - undecyl-n a43 —0-Nonyl-n a34 Tridecyl-n A44 —0-Decyl-n a35 Decvl-n_ a45 a36 C! - yl-heptyl-N A46 —0 — Undecyl-n a37 ch ₃ o Octyl-t A47 —0 - Dodyl-n a38 C ₂ H ₅ O-Y-Nonyl-n A48 0 - T r class d l-n

Table 1a (continued)

Rest A | Rest A A49 —0-Tetradecyl-n A59 a50 —0-Pentadecyl-n a60 a51 w —0-Hexadecyl-n AOL a52 —0-Heptadecyl-n A62 A53 - ^ - O-n-Octadeeyl A63 A54 —S ^- N onyl-n A64 O ^ 2> b, a55 - ^ 2y-CH-OC ₂ H _s a65 ° C - / - - ° ^{CH 3} a56 CH-O-C ₃ H ₇ -i AOO about —— O - Butyl-n A57 -CH _; —O — C ₄ H-i A67 ^CH 3 ° - —OCH ₃ A58 OO AOS O-Of- CH,

Table 1a (continued)

Rest A Rest A A69 Cl 'O ^{- ci} A78 about- about- -Butyl-N a70 w Cl 4 Y / ^Cl A79 CL__ about- about T-Butyl and 71 Cl / "A ~ Ot ^ci a80 about about -ButyW A72 about- ^ N-pentyl a81 about .it - CHj A73 about- N-octyl a82 about- ABOUT -If A74 “O ^-01 A83 about- about- prop a75 about- ^ N-Propyl A84 och ₃ y c ₂ h « A76 about ~ O- ^Br A85 about- about Sec-butyl A77 about a86 ' about about - Butyl.

Table 1a (continued)

Rest A Rest A A87 CI _y a94 3-n-propyl AS8 & > ~ C _{for 2} h _with A95 ch ₃ / ~ ^CI a89 F y ^F A96 ^C 2 ^H J ° \ \ f / JHci a90 -about Ό -O-CF A97 - / "Λ- CI y- ^Br A91 / ΓΑ_ CI y // - Propyl-n A98 F CI Cl a92 CI y Propyl-i a99. ABOUT -c a93 CI N-propyl Aloo about CI p

Table 1a (continued)

Rest A Rest. A ALOLA Cl AL09 AL02 ^Propyl · al 10 AL03 _CH3 \ _ / in ^ ^CH _CH3 alll <> »- / J c ₂ h ₅ AL04 xhx al! 2 _.F \ Z V at ^ 2 ^ 5 AL05 CH, O /-in all3 al06 -ζΖ) ^- o— al 14 W al07 '0- ^propy, - ⁿ all5 W and? 08 al 16 ch ₃ ch ₃

Table 1a (continued)

Rest A Rest A al 17 ASJ * about AL26 OCH ₃ al 18 ^x - '' - 'ch ₂ al27 —CHj F and? 19 AL28 - ^ ~~ ^ ch ₂ h ^^ ci AL20 -0-0 al29 CL · _ - (ς 2 “ch ₂ - ^” \ Cl AL21 ΟΌ AL30 -Η ^ ΟΗ, ΟΗΓθ-α aL22 aI31 _.Cl yl ~ yl-CH ₂ - p ^ al23 - ^ - ^ - ch ₂ - ^ AL32 ch ₂ -f ^ c AL24 —CH3 Propyl-i AL33 ^CH : Butyl-t and? 25 F - ^ _ —C (CH 3) -Y-Butyl-t and? 34 CH 3 Octyl-n

Table 1a (continued)

Rest A Rest A and? 35 —CH j Octyl-n al44 θ ^8υί ^ ' ^η al36 rf al45 0 —Buty i-sec AL37 ^>^CH'O al46 -0 - ^ - n-hexyl al38 o ° o. al47 0 —Dod ecy i-n and? 39 Ό ° ~ θ and? 48 - ^ ~ ^ O- ^ ~~ ^ O-i-hexyl AL40 -O-CH ₃ al49 -θ-ο-θ-α AL41 _ch ₃ —0 —ch ₃ and? 50 Cl θ ο-θ-α al42 —O —och ₃ and? 51 Sec-butyl _θ-ο-α-ΛΛ and? 43 O-n-propyl and? 52 Υ · ν ₀ _ ^ Λ _C1

Table 1a (continued)

Rest A Rest A al53 Cl -? - O -? - CF ₃ al61 —OCH2; al54 ' F -, _. CL_ —0- (^y ^ -CF-), and? 62 —OCH, pnc al55 -> - o / ~> o-cf ₃ Al63 OOC ^ c ,, al56 -0 - ^ - Br al64 _ΛΗ ₃ ^ ₂ Joch -qc ₂ hours ₅ and? 57 OO AL65UT Stone 0 = 0/3 T and? 58 -OCH ^ C. and? 66 AL59 al67 —OCH2Butyl-t and? 60 —Och ₂ - ^ Cl and? 68 —OCH2 - Propyl

Table 1a (continued)

Rest A Rest A and 169 Cl AL75 -OO à and? 70 O-S AL76 ^X - ch ₃ al71 —OCH ^ F and? 77 Cl al72 al78 Cl - <^ f -OCF, Cl and? 73 Cl Cl and? 79 C! Cl and? 74 Cl Cl and? 80 Cl 'C:

Table 1a (continued)

Table 1a (continued)

Rest A Rest A F j F al93 m ^CFs al95 -d- rf F F r ~ \ F F Cl The F F and? 94 a3 ^ci and? 96 / 5 \ F F F

Further, A may be a residue of the following formula a197 in which

E represents an optionally substituted alkanediyl group and X represents a hydrogen atom or a halogen atom.

The following alkanediyl radicals E are preferred

E1 -cf ₂ - E3 -CFCl- E5 -CF (CH3 ₎ - E7 -C (CH ₃ ) (CH ₂ F) - E9 -C (CH ₃ ) (CH ₂ Cl) - Eli -C (CF ₃ ) (CHCl ₃ CF ₃ ) E13 -CH (CH ₂ CF ₃ ) - E15 CH (CHClCF ₃₎ -

E2 -CF (CCI, CF ₃₎ - E4 -cf ₂ -cf ₂ E6 -CF, -CFCl- E8 -CF, -C (CH ₃₎ - E10 -CF, -C (CH ₃ ) ₂ - E12 -CFCI-CFCl- E14 -CF ₂ -CH (CH ₃ ) - E16 -CF ₂ -CH (CF ₃ ) -

By way of example, the following radicals may be mentioned for substituents B:

bl C1CH ₂ -C (CH ₃ ) ₂ - b6 (CH ₂ Cl) ₃ C- b2 FCH ₂ -C (CH ₃ ) ₂ - B7 CH ₃ -C (CH ₂ OCH ₃ ) ₂ - B3 CH ₃ -C (CH ₂ Cl) ₂ - B8 NC-CH ₂ CH ₂ -C (CH ₃ ) ₂ - b4 CH ₃ -C (CH ₂ F) ₂ - B9 CH ₃ -C (C ₂ H ₃ ) (CH ₂ OCH ₃ ) - b5 Cl ₂ C = CCl- BLO f ₂ ch = cfci- beat Cl ₂ C = CF- BL5 c, -Qo-c ₍ ch3 _{) j} - BL2 F F 4 CH BL6 Cl F 4 CH ₃ b! 3 Δ. Cl BL7 δ_ BL4 Cl Cl c ₂ h ₅ BL8 CH, CH ₃ Cl ₂ C: CH

For the divalent radical Z, for example, the following meanings can be given:

-CH ₂ - -CH (CH ₃ ) -, -CH ₂ CH ₂ -, -CH = CH =, -CH ₂ O-, -CH ₂ S-, -CH (CH ₃ ) S-, -CH (CH ₃ ) O-, CH ₂ CH ₂ O-, -CH ₂ S (O) - and CH ₂ -SO ₂ -.

The preparation of oxazolines of the formula I is known in principle. They can be made by

a) reacting amino alcohols of formula II ^h = ⁿ -c ^zA and R

Lh W

HO _'H in which A and R as defined above, with a carboxylic acid of formula III

B-COOH (III), in which B is as defined above, and with water-withdrawing agents, optionally in the presence of a diluent, or

b) reacting the amide alcohols of formula IV

A /

B-CO-NH-C-R

C ^H

H ° (IV) in which A, B and R are as defined above, with water-withdrawing agents, optionally in the presence of a diluent, or

c) amide derivatives of the general formula V

A

B-CO-NH-C-R

wherein A, B and R are as defined above and

X is a leaving group such as a halogen atom, an alkylsulfonyloxy group or an arylsulfonyloxy group, reacted with a base, optionally in the presence of a diluent.

I

The amino alcohols used in process (a) of the present invention for the preparation of compounds of formula I as starting materials are known and / or can be prepared by known methods by reduction of the corresponding amino acids (see Heterocycles 9 (1978), 1277-1285, J. Org. Chem. 43 (1978), 2539-2541; Liebigs Ann. Chem. 1980, 122-139; Tetrahedron Lett. 26 (1985), 4971-4974).

The carboxylic acids of the formula III, further used as starting materials in carrying out process (a) of the present invention for the preparation of the compounds of the formula I, are known organic synthesis chemicals or are obtainable by known methods.

Methods (a) and (b) of the present invention are carried out using water-withdrawing agents. Conventional water-withdrawing agents may be used herein in organic chemistry. Preferably, sulfuric acid, polyphosphoric acid (PPS), phosphorus pentoxide, dicyclohexylcarbodiimide (DCC), phosphorus pentasulfide and the triphenylphosphine / triethylamine / carbon tetrachloride system are useful.

Suitable diluents for carrying out processes (a) to (c) according to the invention are customary organic solvents. Preferred are aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons such as, for example, benzene, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform and carbon tetrachloride, ethers such as diethyl ether, dioxan-propyl , tetrahydrofuran, ethylene glycol dimethyl ether and ethylene glycol diethyl ether, ketones such as acetone, butanone or methyl isobutyl ketone, nitriles such as acetonitrile, propionitrile or benzonitrile, amides such as N, N-dimethylformamide and Ν, Ν-dimethyl acetamide, hexamethylphosphoric acids, esters such as ethyl acetate, sulfoxides such as dimethyl sulfoxide, and optionally also alcohols such as methanol and ethyl alcohol.

In carrying out process (a) of the present invention, the reaction temperatures can be varied within a wide range. In general, the reaction is carried out at a temperature in the range of 0 ° C to 150 ° C, preferably 10 ° C to 100 ° C.

The process (a) according to the invention is carried out generally under normal pressure, but it is also possible to work at a reduced or elevated pressure, for example in the range from 0.01 to 1.0 MPa.

In carrying out process (a) of the present invention, the necessary starting materials are generally used in approximately equimolar amounts. However, it is also possible to use one of the two starting components used in large excess. The reactions are generally carried out in a suitable diluent in the presence of a water-borne reagent and the reaction mixture is stirred for several hours at the desired temperature. Work-up of the reaction mixture is carried out by conventional methods.

In a particular embodiment of process (a) according to the invention, the corresponding nitriles can also be used instead of the carboxylic acids of the formula III, whereupon a catalyst such as zinc chloride is preferably used instead of the water-withdrawing agent.

The amide alcohols used as starting materials in process (b) of the present invention for the preparation of compounds of formula I are known and / or can be prepared by known methods.

The amide alcohols of the formula I are obtained, for example, by reacting the acid chlorides derived from the carboxylic acids of the formula III with amino alcohols of the formula II in the presence of acid binders such as triethylamine, pyridine, potassium carbonate, sodium hydroxide or tert. potassium butylate and in the presence of diluents, such as toluene, chlorobenzene, acetone or acetonitrile, at a temperature ranging from 0 ° C to 100 ° C.

The acid chlorides derived from the carboxylic acids of the formula III are known and / or can be prepared by known methods, for example by reacting the carboxylic acids of the formula III with halogenating agents such as thionyl chloride, optionally in the presence of a diluent.

The alpha-fluoro-beta-beta-dichloro-alkyl chloride of formula VI is obtained, for example, by hydrolyzing 2-fluoro-1,1,3,3,3-pentachloropropene, optionally in the presence of a catalyst. Suitable catalysts include, but are not limited to, Lewis acids and inorganic acids, and salts thereof, such as, for example, ferric chloride, boron trifluoride, sulfuric acid, hydrochloric acid, potassium hydrogen sulphate and sodium hydrogen sulphate.

Depending on the reaction conditions, such as the residence time of the acid chloride in the reaction mixture and the added amount of water, the primarily formed alpha-fluoro-beta-beta-dichloro-acrylic chloride is optionally hydrolyzed to the corresponding acrylic acid, which is then e.g. can be converted to acid chloride by reaction with thionyl chloride.

In carrying out process (b) of the present invention, the reaction temperatures can be varied within a wide range. In general, temperatures of -20 ° C to 150 ° C, preferably 0 ° C to 100 ° C, are employed.

The process (b) of the present invention is carried out generally under normal pressure, but it is also possible to operate at a reduced or elevated pressure, for example in the range of 0.01 to 1.0 MPa.

In carrying out process (b) according to the invention for the production of the compounds of the formula I, generally 1 to 20 mol, preferably 1 to 5 mol, of a water-removing agent are used per mole of amide alcohol of the formula IV.

In a preferred embodiment of process (b) according to the present invention, the amide alcohol of the general formula IV is introduced in a diluent and then the water-withdrawing agent is metered in. The reaction mixture is stirred at the desired temperature until the reaction is complete and then worked up as usual.

The amide derivatives used as starting materials in process (c) of the present invention for the preparation of compounds of formula I are known and / or can be prepared by known methods.

The amide derivatives of formula V are obtained by reacting the corresponding amide alcohols of formula IV with chlorinating agents, such as thionyl chloride or phosphorus pentachloride, optionally with sulfonating agents, such as methanesulfonic acid chloride or ptoluenesulfonic acid chloride, in the usual manner, optionally in the presence of a base and optionally in the presence of a diluent.

Process (c) according to the present invention is carried out in the presence of a base, wherein all customary inorganic or organic bases are suitable. Preferred are the hydrides, hydroxides, amides, alcoholates, acetates, carbonates or bicarbonates of the alkaline earth metals or alkali metals such as sodium hydride, sodium amide, sodium ethylate, sodium methylate, potassium tert-butylate, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or ammonium carbonate, as well as tertiary amines such as trimethylamine, triethylamine, tributylamine, N, Ndimethylaniline, pyridine, N-methylpiperidine, Ν, Ν-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).

In carrying out process (c) of the present invention, the reaction temperatures can be varied within a wide range. In general, temperatures of -20 ° C to 150 ° C, preferably 0 ° C to 100 ° C, are employed.

The process (c) of the present invention is carried out generally under normal pressure, but it is also possible to operate at a reduced or elevated pressure, for example in the range of 0.01 to 1.0 MPa.

In carrying out process (c) according to the invention for the preparation of the compounds of the formula I, generally 1 to 3 mol, preferably 1 to 1.5 mol, of base are used per mole of amide derivative of the formula V.

In a preferred embodiment of process (c) of the present invention, the amide derivative of formula V and the base are mixed in a suitable diluent, stirred at the desired temperature until the reaction is complete, and then worked up in the usual manner.

The active substances are, with good toxicity to warm-blooded animals, suitable for controlling pests in animals, in particular insects and mono-host ticks, which occur in the rearing and cultivation of animals such as livestock, breeding animals, zoo animals, experimental animals and animals kept for livestock. . They are effective against normally sensitive and resistant species as well as against all or individual developmental stages.

The control of pests in animals is intended to combat diseases and their transmission, deaths and performance degradation (for example, in the production of meat, milk, wool, skin, eggs and the like), so that the use of active substances makes animals more economical and easier to use. only now enabled.

Pests include:

From the Anoplura class, for example, Haematopinus s p., Linognathus spp., Solenopotes spp., Pediculus spp.

From the Mallophaga class, for example, Trimenopon spp., Menopon spp., Eomenacanthus spp., Menacanthus spp., Trichodectes spp., Felicola spp., Damalinea spp., Bobiola spp., Trinoton spp., Verneckiella spp., Lepikeutron spp.

From the Diptera class, for example, Crysops spp., Tabanus spp., Musca spp., Hydrotaea spp., Muscina spp., Haematobosca spp., Haematobia spp., Stomoxys spp., Fannia spp., Glossina spp., Lucilia spp., Calliphora spp. , Auchmeromyia spp., Cardylobia spp., Cochiomyia spp., Chrysomyia spp., Sarcophaga spp., Wohlafartia spp., Oesteromyia spp., Oedemagena spp., Hypoderma spp., Oestrus spp., Rhinoestrus spp. Melophagus spp., Hippobosca spp.

From the Siphonaptera class, for example, Ctenocephalides spp., Echidnophaga spp., Ceratophyllus spp., Pulex spp.

From parasitic living ticks the following genera and species:

Hyalomma spp., Rhipicephalus evertsi, Boophilus spp., Amblyomma spp., Dermacentorspp., Ixodes ricinus, Argas spp., Ornithodorus spp., Otobius spp.

From the class of Mesastigmata Dermanyssus spp., Pneumonyssus spp.

From the Prostigmata class, for example, Cheyletiella spp., Psorergtes spp., Myobia spp., Demdex spp., Neotrombicula spp.

From the Astigmata class, for example, Acarus spp., Myocoptes spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Notoedres spp., Knemidocoptes spp., Neoknemidodoptex spp., Lytodites spp., Laminosioptes.

In particular, the action of the compounds of the formula I against single-host ticks should be emphasized. These include Boophilus spp. and Hyalomma spp.

Breeding and productive animals include mammals such as cows, horses, sheep, pigs, dogs, cats, goats, camels, water buffaloes, donkeys, rabbits, fallow deer, reindeer and fur animals such as mink, chinchilla and raccoon; birds such as chickens, geese, turkeys and ducks.

Laboratory and experimental animals include mice, rats, guinea pigs, hamsters, dogs and cats.

The animals raised for pleasure include dogs and cats.

The administration of the active compounds can be carried out both prophylactically and therapeutically.

The application of the active substances is carried out directly or in the form of suitable preparations by enteral, parenteral, dermal, nasal, environmental treatment or by means of shaped bodies containing the active substance, such as strips, pads, belts, collars, ear tags, limb belts and marking devices .

Enteral administration of the active ingredient is carried out, for example, orally in the form of powders, tablets, capsules, pastes, beverages, granules, orally administrable solutions, suspensions or emulsions, medicated feed or drinking water. Dermal application is carried out, for example, by dipping, spraying, bathing, washing, pour-on and spot-on and powdering. Parenteral administration is by injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.

Suitable preparations include:

Solutions such as injectable solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or body cavities, glazing preparations and jellies.

Emulsions and suspensions for oral or dermal administration as well as for injection, semi-solid preparations.

Preparations in which the active substance is incorporated in an ointment base or in an oil-in-water or water-in-oil emulsion base.

Solid formulations, such as powders, premixes or concentrates, granules, pellets, tablets, capsules, aerosols and inhalants, active ingredient-containing melters.

Injectable solutions are administered intravenously, intramuscularly and subcutaneously.

Injectable solutions are prepared by dissolving the active ingredient in a suitable solvent and adding optional ingredients such as solubilizers, acids, bases, buffer salts, antioxidants and preservatives. The solutions obtained are then sterile filtered and filled.

Solvents include physiologically acceptable solvents such as water, alcohols such as ethyl alcohol, butyl alcohol, benzyl alcohol, glycerol, propylene glycol, and polyethylene glycols, N-methylpyrrolidone hydrocarbons and mixtures thereof.

Alternatively, the active compounds may also be dissolved in the biologically acceptable vegetable or synthetic oils which are suitable for injection.

Diluents which may be mentioned are solvents which promote the dissolution of the active substance in the main solvent or prevent its precipitation. Examples include polyvinylpyrrolidone, polyoxyethylated castor oil and polyoxyethylated sorbitan ester.

Preservatives are, for example, benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid esters and n-butyl alcohol.

Oral solutions are used directly. Concentrates are orally applied upon prior dilution to the desired concentration. Oral solutions and concentrates are prepared as described for injectable solutions, but sterile work may be omitted.

Solutions for application to the skin are dripped, sprayed, sprayed, sprayed, sprayed or dipped (soaking, bathing or washing). These solutions are prepared as described for injectable solutions.

In the manufacture, it may be advantageous to add a thickening agent. Thickening agents include inorganic thickeners, such as bentonites, colloidal silicic acid or aluminum monostearate, or organic thickeners, such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and methacrylates.

Gels are applied or coated on the skin or introduced into body cavities. These gels are prepared by preparing solutions as described for injectable solutions and mixed with an amount of thickening agent to produce a clear mass with an ointment similar in consistency. The thickeners used are those mentioned above.

The pouring means is poured or sprayed onto the delimited areas of the skin, whereby the active substance penetrates the skin and systemically acts or disperses on the body surface.

The pouring compositions are prepared by dissolving, suspending or emulsifying the active ingredient in a suitable skin-acceptable solvent or solvent mixture. Optionally, additional excipients such as colorants, resorption-promoting substances, antioxidants, light preservatives and adhesion promoters may be added.

Solvents include water, alkanols, glycols, polyethylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethyl alcohol or phenoxyethyl alcohol, esters such as ethyl acetate, butyl acetate and benzyl benzoate, ethers such as alkylene glycol such as dipropylene glycol monomethyl ether and diethylene glycol monobutyl ether, ketones such as acetone and methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, dimethylformamide, dimethylacetamide, N-methylpyrrolidone and 2,2-dimethyl-4-oxy-methylene ethylene .

Colorants are all colorants acceptable for use in animals which can be dissolved or suspended.

Resorptive enhancers include, for example, dimethylsulfoxide, oils such as isopropyl myristate and dipropylene glycol pelargonate,? Ilic oils, fatty acid esters, triglycerides, and fatty alcohols.

Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole or tocopherol.

Light-protecting agents include, for example, benzophenones or novantisolic acid.

Adhesion agents are, for example, cellulose derivatives, starch derivatives, polyacrylates, and natural polymers such as alginates or gelatin.

The emulsions may be administered orally, dermally or as injections.

The emulsions are either water-in-oil or oil-in-water.

Said emulsions are produced in such a way that they are effective. the substance dissolves in either the hydrophobic or hydrophilic phase and this is homogenized with suitable emulsifiers and optionally other excipients such as colorants, resorption promoters, preservatives, antioxidants, light preservatives and viscosity enhancers, with the second phase solvent.

Hydrophobic phases (oils) include paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil and castor oil, synthetic glycerides such as caprylic and capric biglyceride, mixtures of triglycerides with vegetable fatty acids of length chains of 8 to 12 carbon atoms or other specially selected natural fatty acids, mixtures of partial glycerides saturated or unsaturated, optionally also hydroxyl groups containing fatty acids or monoglycerides and diglycerides of fatty acids with 8 to 10 carbon atoms.

Further, fatty acid esters such as ethyl stearate, di-n-butyryl adipate, laurinic hexyl ester, dipropylene glycolpelargonate, mid-chain branched fatty acid esters of saturated fatty alcohols of 16 to 18 carbon atoms, isopropyl myristate, isopropyl myristate, isopropyl myristate, / capric acid with saturated fatty alcohols with a chain length of 12 to 18 carbon atoms, oleic acid oleic acid, oleic acid decyl ester, ethyl oleate, ethyl lactic acid ester, waxy fatty acid esters such as duck fatty gland fat, dibutyl phthalate, adisopropyl ester, diisopropyl ester, the latter related esters and the like.

Fatty alcohols such as isotridecyl alcohol, 2-octyldodecyl alcohol, cetyl stearyl alcohol or oleyl alcohol and fatty acids such as oleic acid or mixtures thereof may also be mentioned.

The hydrophilic phase includes:

water and alcohols such as propylene glycol, glycerol, sorbitol and mixtures thereof.

The following emulsifiers are used:

non-ionic surfactants, for example polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate or alkylphenol polyglycol ether, ampholytic surfactants such as di-Na-N-lauryl-sulfonate tinate tinate tinate tinate fatty alcohol or monoethanolamine salt of mono / dialkylpolyglycol ether orthophosphoric acid esters, cationic surfactants such as cetyltrimethylammonium chloride.

Viscosity-enhancing and emulsion-stabilizing agents such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, acacia, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether, and maleic anhydride polymers can be used as additional excipients. waxes, colloidal silicic acid or mixtures thereof.

Suspensions may be administered orally, dermally or as injections. They are prepared by suspending the active ingredient in a carrier liquid, optionally with the addition of additional excipients such as wetting agents, coloring agents, resorptive agents, preservatives, antioxidants, light preservatives and the like.

All homogeneous solvents and solvent mixtures can be used as carrier liquids.

Wetting agents (dispersing agents) which may be mentioned are the surfactants mentioned above.

Substances already mentioned above can be used as further excipients.

Semi-solid preparations can be administered orally or C ^r rmala. They differ from the suspensions and emulsions described above only by their higher viscosity.

In order to produce solid preparations, the active ingredient is mixed with a suitable carrier, if appropriate with the addition of excipients, and converted to the desired form.

Carriers which may be mentioned are all physiologically acceptable solid inert substances. Inorganic and organic substances serve as such. Inorganic substances are, for example, sodium chloride, carbonates such as calcium carbonate, bicarbonates, alumina, silicic acid, clay soils, precipitated or colloidal silicon dioxide or phosphates.

Organic substances are, for example, sugar, cellulose, foodstuffs and feedstuffs such as milk powder, animal meal and cereal flour or scrap or starch.

Excipients are preservatives, antioxidants, colorants and the like, as mentioned above.

Other excipients are lubricants such as magnesium stearate, stearic acid, talc and bentonite, disintegrating agents such as starches or cross-linked polyvinylpyrrolidone, binders such as starch, gelatin or linear polyvinylpyrrolidone, as well as dry binders such as microcrystalline cellulose.

The active compounds may also be present in the formulations in admixture with synergists or other active compounds.

Formulations suitable for application contain the active compound in concentrations of 10 ppm to 20% by weight, preferably 0.1 to 10% by weight.

The preparations which are diluted before use contain the active compound in a concentration of 0.5 to 90% by weight, preferably 5 to 50% by weight.

In general, it has been found advantageous to use about 1 to 100 mg of active ingredient per kilogram of body weight per day to achieve effective results.

DETAILED DESCRIPTION OF THE INVENTION

The active compound 1 used in the following examples is a compound of the formula

2- (2,6-difluorophenyl) -4- [4- (4-trifluoromethoxyphenyl) phenyl] -2-oxazoline

Example I

Suspension Concentrate Preparation (SC)

386 g active substance 1 g block polymer of emulsifier, ethylene oxide and propylene oxide g condensate of ditholylether sulfonate and formaldehyde (emulsifier)

3.5 g water-soluble polyvinyl alcohol

58.0 g ammonium chloride

116.0 g urea

1.2 g 37% aqueous hydrochloric acid

4.6 g xanthan gum

560.5 g distilled water.

Example II

Dispersible Powder Preparation (WP)

250 g active substance 1

1.0 g diisobutyl-naphthalene-Na-sulfonate

Calcium n-dodecylbenzenesulfonate (10.0 g)

12.0 g alkylaryl polyglycol ether containing highly disperse silicic acid 3.0 g ditolylether sulfonate and formaldehyde condensate (emulsifier)

2.0 g ^R Basilon-E, a silicone containing antifoam by Fy. Ba · er AG

2.0 g finely dispersed silica and

45.0 g kaolin.

Example III

Water-soluble concentrate (SL) preparation

18.3 g active substance 1

2.5 g neutral emulsifier based on alkylaryl polyglycol ether

3.5 g of sodium sulphosuccinic acid diisoctyl ester

38.4 g dimethylsulfoxide a

37.5 g of 2-propyl alcohol

Example IV

Water-soluble concentrate (SL) preparation

185 g active substance 1

5.0 g of sodium sulfosuccinic acid diisoctyl ester

76.5 g of dimethyl sulphoxide are mixed with 100 g of a shampoo composition consisting of

44.4% by weight of Marlon AT 50, an alkylbenzenesulfonic acid triethanolamine salt of phy. Hiils AG

II, 1% by weight of Marlon A 350, alkylbenzenesulfonic acid sodium salt of phy. Hiils AG

3.0% by weight of a condensation product of oleic acids and diethanolamine from. Hils AG a

41.5% by weight of polyethylene glycol.

Example V

Spray preparation

2,0 g active substance 1

10.0 g of dimethylsulfoxide

35.0 g of 2 - propyl alcohol and

53.0 g acetone

Production examples

Example 1

To 1 g (6 mmol) of 4-tert-butyl-thiophenol in 50 ml of methanol was added with stirring 0.3 g (6 mmol) of sodium methylate (slightly exothermic reaction). To this solution was added dropwise at 40 ° C 2.1 g (6 mmol) of 2- (2,6-difluorophenyl) -4- (ptolylsulfonyloxymethyl) -1,3-oxazoline in 30 ml of methanol and the reaction mixture was allowed to stir for for 2 hours at 40 ° C and then for 16 hours at reflux. The solvent is distilled off, the residue is taken up in 100 ml of ethyl acetate and washed three times with 50 ml of water each time. The solvent is then stripped off and the residue is purified by column chromatography on silica gel using toluene / toluene, ethyl acetate 10: 1.

0.9 g (41.6% of theory) of 2- (2,6-difluorophenyl) -4- (4-tert-butylphenylthiomethyl) -1,3-oxazoline is obtained with a dispersion coefficient of log P (octanol / water). = 4.64 and refractive index no ²⁰ = 1.5660.

Preparation of the starting compounds Example 1a

F

CH, -O-SO

To 5.3 g (0.023 mol) of 2- (2,6-difluorophenyl) -4-hydroxymethyl-1,3-oxazoline in 100 ml of ethyl acetate was added 5.6 ml (0.069 mol) of pyridine and then added dropwise.

4.4 g (0.023 mol) of p-toluenesulfonic acid chloride in 50 ml of ethyl acetate. The temperature rises to 50 ° C. The reaction mixture was stirred for 2.5 hours at 50 ° C and then for 8 hours at reflux. The organic phase is washed four times with 50 ml of water each time and the solvent is distilled off. The residue is purified by column chromatography using toluene with a gradient of ethyl acetate.

2.1 g (24.8% of theory) of 2- (2,6-difluorophenyl) -4- (p-toluenesulfonyloxymethyl) -1,3-oxazoline are obtained with a dispersion coefficient of log P (octanol / water) = 2, 68 and refractive index no ²⁰ = 1.5491.

Example 1b

CH, OH ·

6.5 g (0.0168 mol) of N- [1-chloro-3- (4-tert-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide are dissolved in 100 ml of methanol and 2 ml (0.033 mol) are added. 45% sodium hydroxide and the reaction mixture is allowed to stir for 4 hours at reflux. After distilling off the solvent, the residue is taken up in 100 ml of ethyl acetate, washed three times with 50 ml of water each time and the solvent is distilled off.

2.8 g (72% of theory) of 2- (2,6-difluorophenyl) -4-hydroxymethyl-1,3-oxazoline of melting point 82 DEG C. are obtained.

Example 1c

^C (CH3) ₃ g (0.023 mol) of N- [1-hydroxy-3- (4-tert-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide are suspended in 60 ml of carbon tetrachloride, mixed with 1, 7 ml (0.023 mol) of thionyl chloride are added and the reaction mixture is heated at reflux for 1.5 hours, after which time the solvent is distilled off.

9.3 g of N- [1-chloro-3- (4-tert-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide are obtained with a dispersion coefficient of log P (octanol / water) = 3.86.

Example 1d

CO-N chh-ch ₂ -o-co

CH-OH

C _{(CH3) 3}

To 21 g of 2-amino-3- (4-tert-butylbenzoyloxy) -1-propanol hydrochloride in 400 ml of ethyl acetate are first added 21.9 ml (0.158 mol) of triethylamine and then added dropwise at 0 ° C 13, 9 g of 2,6-difluorobenzoic acid in 20 ml of ethyl acetate. The reaction mixture is allowed to stir for 1 hour at 20 ° C, the precipitate formed is filtered off with suction, the organic phase is washed three times with 100 ml of water each time, the solvent is distilled off and the residue is stirred with diisopropyl ether.

After drying, 14 g (48% of theory) of N- [1-hydroxy-3- (4-tert-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide are obtained with a dispersion coefficient of log P (octanol / water) = 2 , 82nd

Example 2

C _{(CH3) 3}

To 4.3 g (0.013 mol) of N- [2-chloro-1- (4-tert-butylphenyl) ethyl] -2,2-bis (fluoromethyl) propionic acid amide in 100 ml of methanol is boiled under 1.6 ml (0.026 mol) of 45% sodium hydroxide in 5 ml of water are added dropwise to the reflux condenser and the reaction mixture is allowed to stir at reflux for one hour. The mixture is concentrated by evaporation of the solvent, the residue is stirred with water and the precipitate is filtered off with suction and dried.

3.8 g (99% of theory) of 2- (1,3-difluoro-2-methyl-prop-2-yl) -4- (4-tert-butylphenyl) -1,3-oxazoline, m.p. 62 - 63 C.

Preparation of the starting compounds of Example 2

Example 2a (level 1)

CH, F

HO-CH

To 3.9 g (0.02 mol) of 2-amino-2- (4-tert-butylphenyl) -1-ethanol in 150 ml of ethyl acetate is added 3.3 ml (0.02 mol) of triethylamine and then the mixture was stirred dropwise at 0 ° C with 3.7 g (0.024 mol) of 2,2-bis (fluoromethyl) propionic acid chloride. The reaction mixture was then allowed to warm to room temperature and stirred overnight. The precipitate formed is filtered off with suction, the filtrate is washed several times with water, the organic phase is separated, dried over sodium sulphate, filtered and concentrated.

4.5 g (71.9% of theory) of N- [2-hydroxy-1- (4-tert-butyl-phenyl) -ethyl] -2,2-bis- (fluoromethyl) -propionic acid amide, m.p. 141 ° C.

Example 2b (Stage 2)

CH

CH ₂ F -CO-NH

CH ₂ F

CH

I

CI-CH

Smell)

To 4.5 g (0.0144 mol) of N- [2-hydroxy-1- (4-tert-butylphenyl) -ethyl] 2,2-bis- (fluoromethyl) -propionic acid amide (see step 1) in 100 ml of carbon tetrachloride are added with 1.05 ml (0.0144 mol) of thionyl chloride and the reaction mixture is allowed to react for one hour at reflux. After distilling off the solvent, 4.3 g (90% of theory) of N- [2-chloro-1- (4-tert-butylphenyl) -ethyl] -2,2-bis (fluoromethyl) -propionic acid amide, m.p. 98 ° C.

Example 3

To a solution of 2.0 g (5.2 mmol) of N- [1- (4-tert-butylphenyl) -2-chloroethyl] -2,3,5,6-tetrafluorobenzoic acid amide in 30 ml of tetrahydrofuran is added 0.75 g ( Potassium tert-butylate (6.7 mmol) and the reaction mixture was stirred at 50 ° C. After 3 hours, the mixture was poured into water and extracted with methylene chloride. The organic extract was washed with water, dried over anhydrous magnesium sulphate and concentrated in vacuo. The residue is purified by column chromatography (chloroform).

0.8 g (44.7% of theory) of 4- (4-tert-butylphenyl) -2- (2,3,5,6-tetrafluorophenyl) -1,3-oxazoline is obtained with a dispersion coefficient of log P (octanol / water) = 4.70 (pH 7.4).

Preparation of the starting compounds of Example 3 Example 3a

C _{(CH3) 3}

2.1 g (5.7 mmol) of N- [1- (4-tert-butylphenyl) -2-hydroxyethyl] -2,3,5,6-tetrafluoro-benzoic acid amide was heated in 50 ml of toluene with 5 ml of thionyl chloride. reflux for 18 hours. Excess thionyl chloride and solvent are then evaporated in vacuo.

2.2 g (100% of theory) of N- [1- (4-tert-butylphenyl) -2-chloroethyl] -2,3,5,6-tetrafluorobenzoic acid amide are obtained and are reacted directly.

Example 3b

To a solution of 1.45 g (7.5 mmol) of 2-amino-2- (4-tert-butylphenyl) -ethanol and 0.75 g (7.5 mmol) of triethylamine in 20 ml of methylene chloride is added dropwise with stirring at temperature 20 DEG C. 1.6 g (7.5 mmol) of 2,3,5,6-tetrafluorobenzoyl chloride dissolved in 10 ml of methylene chloride. The reaction mixture is boiled overnight, diluted with methylene chloride, washed with water and the organic phase concentrated in vacuo. The residue is stirred with a small amount of n-pentane and filtered off with suction.

2.3 g (83.1% of theory) of N- [1- (4-tert-butylphenyl) -2-hydroxyethyl] -2,3,5,6-tetrafluorobenzoic acid amide, m.p. 158 DEG-160 DEG, are obtained. C.

Example 4

3.4 g (8.7 mmol) of 2-phenyl-5- (2,6-dichlorobenzoyl-amino) -5-hydroxymethyl-1,3-dioxane are suspended in 50 ml of toluene and stirred with 2 g of thionyl chloride for 24 hours at 80 ° C. Thereafter, excess thionyl chloride and toluene are distilled off under a water pump vacuum.

The residue is taken up in 50 ml of toluene and treated with 0.9 g of potassium tert-butylate. The reaction mixture was then stirred under TLC at 50 ° C. After complete reaction, the solution obtained is washed with water and the organic phase is then concentrated under a water pump vacuum. The residue is chromatographed on silica gel with cyclohexane / ethyl acetate (2: 1).

1 g (31% of theory) of 8-phenyl-2- (2,6-dichlorophenyl) 1-aza-3,7,9-trioxaspiro [4.5] dec-1-ene is obtained, m.p. 158-160 ° C. .

Preparation of the starting compounds for Example 4 Example 4a

C _{(CH3) 3}

104 g (0.35 mol) of 2- (4-tert-butylphenyl) -5-hydroxymethyl-5-nitro-1,3-dioxane are mixed in 1 l of ethanol with 10 ml of triethylamine and 10 g of palladium on carbon and the mixture is hydrogenated for 3 days at 20 ° C and 3 bar. The catalyst is filtered off, the filtrate is concentrated under a water pump vacuum, the residue is

- digested with n-hexane, the crystalline product being isolated by suction.

43 g (47% of theory) of 2- (4-tert-butyl-phenyl) -5-hydroxymethyl-5-amino-1,3-dioxane are obtained, m.p. 138-140 ° C.

Example 4b

C _{(CH3) 3} g (20 mmol) of 2- (4-tert-butyl-phenyl) -5-amino-5-hydroxymethyl-1,3-dioxane in 80 ml of methylene chloride was treated with 5 ml of triethylamine. A solution of 4.5 g (20 mmol) of 2,6-dichlorobenzoyl chloride in 5 ml of methylene chloride was added dropwise at 0 ° C and the reaction mixture was stirred for 15 hours at 20 ° C. It is then washed with 0.5 N sodium hydroxide, the organic phase is separated, dried over sodium sulphate and filtered. The filtrate is concentrated in a water pump vacuum, the residue is crystallized by digestion with n-hexane and the product is isolated by suction filtration.

7.2 g (83% of theory) of 2- (4-tert-butyl-phenyl) -5-hydroxymethyl-5- (2,6-dichloro-benzoylamino) -1,3-dioxane are obtained, m.p. 178 to 180 ° C.

Example 5

F

0.67 g (2 mmol) of N- (2-hydroxy-1- (3,4-difluoromethylenedioxyphenyl) -ethyl) -2,6-difluorobenzamide are added to 15 ml of toluene and 0 ° C is added at 0 ° C. 27 ml (4 mmol) of thionyl chloride. The reaction mixture is then heated at reflux for 3 hours. After cooling, it is concentrated, the residue is taken up in 15 ml of tetrahydrofuran and, after addition of 0.23 g (2 mmol) of potassium tert-butylate, the mixture is stirred for one hour at 50 ° C. It is then concentrated, the residue is taken up in a mixture of methylene chloride and water, the organic phase is dried over anhydrous magnesium sulphate and filtered. The filtrate is concentrated and the residue is recrystallized from methylene chloride / petroleum ether.

0.13 g (20% of theory) of 2- (2,6-difluorobenzoyl) -4- (3,4-difluoromethylenedioxyphenyl) -2-oxazoline is obtained, m.p.

Preparation of the starting material of Example 5

Example 5a

2.31 g (10 mmol) of alpha-amino-alpha- (3,4-difluoromethylenedioxyphenyl) acetic acid are introduced with 0.91 g (24 mmol) of sodium borohydride into 30 ml of tetrahydrofuran at 0 ° C and then after a solution of 3.05 g (24 mmol) of iodine in 10 ml and tetrahydrofuran was added dropwise. After gas evolution had ceased, the reaction mixture was refluxed for 16 hours. After cooling, it is diluted with methanol until a clear solution is formed, then concentrated, taken up in 20 ml of 20% sodium hydroxide and extracted three times with 50 ml of methylene chloride each time. The combined organic phases were dried over anhydrous magnesium sulfate and filtered. After evaporation of the filtrate, the product obtained as a residue is further reacted without further purification.

1.52 g (70% of theory) of melting point 70 DEG C. are obtained.

Example 5b

1.0 g (2 mmol) of N- [2- (2,6-difluorobenzoyloxy) -1- (3,4-difluoromethylenedioxyphenyl) ethyl] -2,6-difluorobenzamide was added to 2 ml of methyl alcohol at 2 ml of 1 N sodium hydroxide are added at 20 ° C and the mixture is heated under reflux for one hour. After cooling, the mixture is shaken three times with 50 ml of methylene chloride each time, the organic phases are combined, dried over anhydrous magnesium sulphate and filtered. The filtrate was concentrated and the crude product obtained as a residue was reacted further without further purification.

0.67 g (93% of theory) of melting point 158 DEG C. is obtained.

In accordance with the examples given in the general production data, the compounds of formula I (I) shown in the following table are obtained:

table

PR. B A R t, t. (° C) 6 4 F T CH, - ^ ~ / ~ ^CF3 H 128-31 7 4 F H 117 ί 4 F ^CF 3 OCF ₃ H 65-68 9 4 F F · ocf ₃ H 106-08

Claims (4)

PATENT CLAIMS Use of oxazolines of the general formula I (I) in which B represents an optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl group, A represents an aryl group, an aryloxy group or a heteroaryloxy group which are optionally substituted and which are optionally linked via a bivalent radical Z to an oxazoline ring and R represents a hydrogen atom or, together with A and the adjacent carbon atom, a spirocyclic three to six membered ring, which may optionally contain one or more heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen and to which an additional fused may be optionally. a ring, wherein the system is optionally substituted, for controlling parasitic insects and mono-host ticks in humans and animals. A composition against parasitic insects and monocotyledons in humans and animals, characterized in that it comprises at least one compound of the formula I according to claim 1. Process for the preparation of a composition against parasitic insects and monostable ticks in humans and animals, characterized in that the compounds of the formula I according to claim 1 are mixed with fillers and / or surfactants. Use of the compounds of the general formula I according to claim 1 for the production of compositions against parasitic insects and monostable ticks in humans and animals.