IL44345A - Cyclopropyl methanol and cyclopropyl carboxylic or thiocarboxylic acid esters - Google Patents

Description

atDinn 791 V srto >»Di*re >p«i re OIIOOR n^op^naipi'n m n»7»opmaip V»Dii» >p»xn CTCLOFfiO JL HEEHfiSOL ADD CTOLQPRQPTL CABBCKTLIC (fi THIOCARBGXTLIC ACID ESTERS This Invention relates to novel compounds, syntheses thereof, compositions thereof, and the control of mites.

The compounds of the present invention are effective for the control of mites and especially spider mites. Spider mites are plant feeders and cause serious damage to orchard trees, field crops, greenhouse plants and other vegetation. They have a vide distrit " - ° feed on the foliage or fruit of plants and trees of an extensive variety of plants and trees. Spider mites of the family Tetranychidae, such as Tetranychus urticae. Tetranychus canadensis. Tetranychus cinnabarlnus. Tetranychus pacificus. Bryobia praetiosa. Oligonychus pratensis.

Olifionychus ilicis. Panoavchus citri. Panonychus ulmi. and similar relates species, are of particular biological interest and economic importance. Other mites are those of the family Tarsonemidae, such as Steneotarsonemus palllduB.

Compounds of the present invention of the following formulae A, B and C are effective control agents for mites* 0 0 0 |^(CH2)n-C-0-(R p-A-(R p^-C-(CH2)n-- ^| (B) wherein X is -0- or -S-; R is alkyl of ten to twenty-two carbon atoms, alkenyl of ten to twenty-two carbon atoms, or alkynyl of ten to twenty-two carbon atoms; R' is alkylene of one to six carbon atoms; A is alkylene of up to twenty carbon atoms, alkenylene of two to twenty carbon atoms, alkynylene of two to twenty carbon atoms, cycloalkylene having from four to six carbon atoms in the ring, or arylene of six to twenty carbon atoms; A' is cycloalkylene having from four to six carbon atoms in the ring, or arylene of six to twenty carbon atoms optionally-substituted by one or two alkyl, halogen or nitro groups; n is zero or a positive integer from one to four; and p is zero or one; with the proviso that when A' is 1,4-phenylene, p is one* For compounds of formula A i is preferred that R is alkyl, alkenyl or alkynyl.

For compounds of formula B, in one class of preferred compounds n is zero and A is alkylene. n another class, n is two and A is alkylene, cycloalkylene or arylene notably cyclohexylene, or p-phenylene. In a further class A is 1 ,3-cyclobutylene, 1 ,3-cyclopentylene or 1 ,4-cyclohexylene» Preferably then n is zero or two.

In a particularly preferred compound in this group n is zerrj^ X--i-e--«.a-> , p is one, * is methylene and A is 1 , 4~cyclohexylene . In a still further preferred class of compounds of formula B, —€>-, A is arylene, n is zero, p is one and R' is methylene. For compounds of formula B or of formula C, it may be preferred that R' is ~CH2~ , and A and A' are arylene with the proviso that itfhen A' is 1 , 4-phenylene , p is one, or that A or A* is cyclobutylene, cyclopentylene or cyclohexylene, aaek-sufe- In a preferred class of compounds of formula C, X—i-s— , R' is methylene when p is one, and A' is 1,4-phenylene, 2,5-dimethy1-1,4-phenylene, T , ' -biphenylene , 2 , 5-dichloro-l, 4-phenylene, or 2-nitro-l, 4-phenylene. In another (overlapping) class, X is -0-, p is aero and A' is 2, 5-dimethy1-1,4-phenylene, r, 4 '-biphenylene, 2, 5-dichloro-l, -phenylene or 2-nitro-l ,4-phenylene.

In a further preferred class, A' is cycloalkylene of four to six carbon atoms, optionally substituted by one or more alkyl, alkoxy or halogen groups. Preferably ihen A is optionally substituted cycloalkylene, X is oxygen and R' is methylene, ethylene, trimethylene or tetramethylene.

Hereinafter, each of X, R, R* , n, p, A and A' is as defined above unless otherwise specified.

The compounds of formulae A, B and C are applied to the mite at the egg, larval, or nymphal stages in view of their effect in causing inhibition of ogg hatching, abss©rmal development leading to death, inability to pass from one stage to the next, or inability to reproduce. Some of the .compounds also exhibit a residual ovicidal effect. A compound of formula A, D or C may be applied at concentration levels of the order of 0.001^ to I'/ , usually 0.01 to 0.1¾ by weight. Suitable carrier substances Includ liquid or solid inert carriers, such as water* aootono, xylene, mineral or vegetable oils, talc, veroi-oulite, and silica. Control of mites in accordance with the present invention can be accomplished by spraying, dusting, or otherwise contacting the mites andor their eggs or larvae directly or indirectly. Generally, a concentration of less than 2¾¾ of active compound in the formulation is used depending on the type of application apparatus. The formulations can include emulsifying agents and vetting agenta to assist in the application and effectiveness of the actlvo ingredient. n U.S. Patent specification 3,236,728 there are described esters very similar to those of the present invention and differing only in that said prior art esters have.a lower alkyl group.

It has now been unexpectedly discovered, however, that in contradistinction to esters containing short chains according to said U.S. Patent which exhibit low ovicidal aotivity the higher molecular weight eeters of the present invention exhibit high ovicidal activity against mites as fully documented and explained in the description and comparative data now appearing in J.Agrlc.Food.Chem. 24, pp. 1023-1024 (1976). - 2b B or C may be applied at concentration levels of the order of 0.001 to \ usually 0.01 to 0.1 °/ot by weight. Suitable carrier substances include liquid or solid inert carriers, such as water, acetone, xylene, mineral or vegetable oils, talc, vermi-culite, and silica. Control of mites in accordance with the present invention can be accomplished by spraying, dusting, or otherwise contacting the mites and/or their eggs or larvae directly or indirectly. Generally, a concentration of less than 25 of active compound in the formulation is used depending on the type of application apparatus. The formulations can include emulsifying agents and wetting agents to assist in the application and effectiveness of the active ingredient'.

In U.S. Patent specification 5,236,728 there are described esters very similar to those of the present invention and differing only in that said prior art esters have; A lower alkyl group.

It has now been unexpectedly discovered, however, that in contradistinction to esters containing short chains according to said U.S. Patent which exhibit low ovlcidal activity the higher molecular weight esters of the present invention exhibit high ovlcidal activity against mites as fully documented and explained in the description and comparative data now appearing In J.Agric.Food.Chem. 24 pp. 1023-1024 (1976). - 2b - The esters of formulae A and B are prepared by reacting the appropriate mono- or di-hydric alcohol, i.e. R-OH or HO-(R')p-A-(R')p-OH, with at least one or two molar equivalents, respectively, of an acid of the formula (^-(C^^COOH or an acid halide thereof. The reaction can be carried out in the absence of a solvent; however, use of a solvent inert to the reaction, such as an ether or hydrocarbon solvent is preferred. The reaction ordinarily proceeds satisfactorily at room temperature, although higher or lower temperatures may be used. If the alcohol is sensitive to mineral acid, the reaction is preferably conducted in the presence of pyridine at low temperature, e.g. at -10°C to 0°C.

Similarly, the thiol esters of formulae A and B can be prepared by reaction of the acid halide >-(CH2)nC0X ' (where X' is chlorine or bromine) with a mercaptan of the formula RSH, RSNa or HS- (R' ) -A- (R1 )p-SH or NaS-(R') -A-(R') -SNa in an organic solvent inert to the reaction and usually in the presence of pyridine.

The esters and thioesters of formula C are prepared by reacting an acid of the formula H0-8-(R1) -A* - (R1) -8-0H or an acid halide thereof wffth at least 2 molar equivalents cyclopropanemethyl alcohol or cyclopropanemethyl hydrosulfide to obtain the corresponding ester or thioester. The reaction proceeds satisfactorily at room temperature, although higher or lower temperatures may be used. The reaction is usually carried out in the presence of pyridine.

Alternatively, the esters may be prepared by ester-ification of a corresponding alkyl ester with the lithium salt of cyclopropanemethyl alcohol or esterification with cyclopropanemethyl alcohol and acid catalyst in an inert solvent.

The acid halides are conveniently prepared by treating^j^- chloride, phosphorus pentachloride , oxalyl chloride, or phosphorus tribromide .

As used herein, the term "alkyl" refers to a straight or branched chain saturated aliphatic hydrocarbon group of from ten to twenty- two carbon atom, such as dodecyl, tetradecyl, octadecyl, hexadecyl and decyl. The term "alkenyl" refers to a straight or branched chain unsaturated aliphatic hydrocarbon group of from ten to twenty-two carbon atoms and having one to three sites of olefinic unsaturation such as octadec-9-en-1-yl, oleyl, linoleyl and eleostearyl. The term "alkynyl" refers to a straight or branched chain aliphatic hydrocarbon group of from ten to twenty- two carbon atoms and having one or two sites of acetylenic unsaturation, such as dec-2-yn-l-yl , dec-3-yn-l-yl , erythrogenyl , and tariryl.

The term "aryl" refers to a monovalent aromatic hydrocarbon group containing from six to fourteen carbon atoms such as phenyl, tolyl, xylyl, mesityl, naphthyl, ethylphenyl, t-butylphenyl and isopropylphenyl . The term "cycloalkyl" refers to a monovalent cycloalkyl group having four to six carbon atoms in the ring such as cyclobutyl, cyclopentyl, cyclohexyl and 2-methylcyclohexyl .

The term "alkylene", unless otherwise modified, refers to a bivalent radical derived from straight or branched chain alkane containing one to twenty carbon atoms. The term "alkenylene' refers to a bivalent radical derived from a straight or branched chain hydrocarbon group of two to twenty carbon atoms and containing one to three sites of olefinic unsaturation. The term "alkynylene" refers to a bivalent radical derived from a straight or branched chain h drocarbon rou of two to twent carbon atoms and containing one or two sites of acetylenic unsaturation .

The term "cycloalkylene" refers to a bivalent radical derived from a cycloalkyl group having four to six carbon atoms in the ring, such as 1 , 3 -cyclobutylene , 1-4-cyclohexylene , and 2-ethyl-1 ,4-cyclohexylene . The term "arylene" refers to a bivalent radical derived from an aromatic group containing six to twenty carbon atoms. The term "alkoxy" refers to the groups methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and t-butoxy.

The following examples are provided to illustrate the syntheses of the compounds of the present invention and the practice of the present invention. Temperature is reported in degrees Centigrade.

EXAMPLE 1 To a stirred solution of 2.25 g. of cyclopropane carboxylic acid chloride in dry benzene, under nitrogen, is added 8 g. of 1-dodecanol. The mixture is stirred overnight, and then diluted with pentane. The reaction mixture is worked up by washing with water and brine and then removing the solvent to yield dodecyl cyclopropanecarboxylate , (Formula A, n=0, X=0, - (CH2)11 (Active substance No. 1) b.p. 99-100° (bath) at 0.03 mm EXAMPLE 2 To a mixture of 0.2 g. of cyclopropane acetic acid, 30 mis. of anhydrous ether, and 1.3 mis. of thionyl chloride (d^Q=1.66), at 24°, is added 0.3 ml^ . of dimethylformamide .

The mixture is stirred for 5 1/2 hours, and the upper layer of the resultant two phase mixture is decanted into another flas all solvent and volatiles are removed by rotary evaporation. To the residue is added 40 mis. of dry ether and 2.19 g. of 1-pentadecanol in 20 mis. anhydrous ether, followed, at 0°, by 1 ml. of anhydrous pyridine (d2Q=0.982). The reaction mixture is allowed to warm to room temperature and stirred overnight.

The product, pentadecyl cyclopropyiacetate , (Formula A, n=l, X= R=-(CH2)14CH3) (Active substance No. 2) b.p. 118-123°C (bath) at 0.04 mm, is isolated by adding water, ether, and pentane to the reaction mixture, separating the organic layer, washing with 3N sulfuric acid, aqueous 15% potassium carbonate, water, and brine, drying over calcium sulfate and removing the solvent The following compounds of Formula A are obtained in the same manner as described in Examples 1 and 2: No. R X n Boiling Melting point°C/mmHg point°C (short path) 1 - CCH2: ΊιαΗ3 -0- 0 99-100/0.03 - 2 -ccH2: ,14CH3 -0- 1 118-123/0.04 - 3 - CCH2: -0- 0 95.5/0.03 - 4 - CCH2:l17CH3 -o- 0 - 32 5 - CCH2: »15CH3 -0- 0 154/0.1 - 6 -(CH2 l8-CH=CH- (CH2)7CH3 -0- 0 159/0.05 - 7 -CH2-( ≡C- CCH2 6CH3 -0- 0 96-97/0.1 - 8 - CCH2; -s- 0 157/0.4 - 9 - CCH2: ,15CH3 -s- 0 - 26-28 10 - CCH2: 'l7CH3 -s- 0 - 38-39 11 - CCH2: -0- >9CH3 0 85/0.1 - 12 - (CH2: )2C≡C- (CH2)5CH3 -0- 0 78-80/0.01 - 13 - CCH2: -0- ,13CH3 2 121-123/0.03 - 14 - (c¾:lllCH3 -0- 2 116/0.05 - 15 - CCH2: )12CH3 -0- 0 87/0.2 - 16 -CCH2; >14CH3 -0- 0 100/0.05 - 17 -(CH2; -0- 0 - 40-41 No. R X n Boiling Melting point°C/mmHg point0£ (short path) 18 -(CH2)9CH3 -0- 2 106-113/0.03 - 19 -CCH2)14CH3 . -0- 2 142-150/0.04 - 20 -(CH2)15CH3 -0- 2 135-152/0.03 - 21. -(CH2)17CH3 -0- 2 168-176/0.04 - 22 -CH(CH3) (CH2)1]LCH3 -0- 0 112-114/0.04 - 23 -(CH2)nCH3 -0- 4 135/0.22 24 -CH2CH(CH3) CCH2)13CH3 -0- 0 150/0.02 - 25 -(CH2)12CH3 -0- 3 130/0.007 - EXAMPLE 3 ' To a mixture of 3.0 g. of 1 , 4-butynediol , 150 ml. of dry diethyl ether, and 16.9 ml. of dry pyridine at 0°, under argon, is added 10.9 g. of cyclopropanecarboxylic acid chloride over a period of ten minutes. The mixture is stirred for two hours and then water and pentane are added. The mixture is washed in turn with aqueous 3N sulfuric acid, aqueous potassium carbonate, water, aqueous saturated cupric sulfate, water, and brine, dried over calcium sulfate and the solvent removed to yield the bis-cyclopropanecarboxylate of 1 , 4-butynediol , (Formula B, n=0, X=-0-, p=0, A=-CH2-C=C-CH2-) (Active substance No. 26) b.p. 108-111° (bath) at 0.05 mm.

The following compounds of Formula B are obtained in the same manner as described in Example 3.

No. p R' A X n Boiling Melting point°C/mmHg point°C (short path) 26 0 - -CH -C≡C-CH7- -0- 0 108-111/0.05 Boiling Melting point°C/mmHg rp>ooiinntt°°CC W 29 0 - -(CH2)12- -0- 0 - 54.5-55 30 0 - -(CH2)10- -0- 0 - 44-44.5 . 31 1 -CH„- (trans).o- 0 - 75-77 32 0 - —00~ -0- 0 - 118.5-120.5 41 0 - -CH,C≡C-CH0- -0- 2 118-123/0.03 43 1 -CH2- -0~ (cis) "°" 51.5-52.5 EXAMPLE 4 To a mixture of 4.0 g. of trans-1 , 4 -cyclohexanedicar- boxylic acid, 60 ml. dry ether, and 4.5 ml. of thionyl chloride at 24° is added 1.0 ml dry dimethyl^formamide . The mixture is then. stirred at room temperature for five days. The upper layer of the resultant biphasic mixture is separated and the solvent removed. To the remaining residue is added 80 ml. dry ether and 4.45 g. of cyclopropanemethyl alcohol. The reaction mixture is cooled to 0°'; 5.6 ml. dry pyridine is added. The reaction mixture is allowed to warm to room temperature and stirred for ten days. A mixture of ether and water is added, the ether layer is separated, and the aqueous layer is extracted twice with ether. The combined organic phases are in turn washed with 2 N sulfuric acid, 10% aqueous sodium carbonate, water, aqueous saturated copper sulfate, water and brine, dried over calcium sulfate, the solvent removed and the pale yellow liquid residue allowed to become crystalline overnight. The crystalline material is separated and distilled (b.p. 123-126° at 0.03 mm) to yield 0.8 ml. of bis (cyclopropanemethyl) 1 ,4-cyclohexane- dicarboxylate (Active substance No. 44).

The following compounds of Formula C are obtained in the same manner as described in Example 4.

No. p R A X Boiling Melting point°C/mmHg point°C (short path) The mite control agents of the present invention can be used alone in an inert agriculturally acceptable carrier substance for the control of mites (Arachnids) or can be used in mixture with insecticides and/or juvenile hormone analogs known in the art to provide a broader spectrum of activity.

The compounds of the present invention are also useful for the control of mites and ticks which are ectoparasitic on animals and birds. The compounds can be applied in either solution or in powder (dust) form in a conventional manner.

The effectiveness of the compounds of the present invention is demonstrated below.

Adults (Tetranychus urticae) are allowed to oviposit for twenty-four hours on castor bean leaf discs (diameter 1 cm.) on moist cottonwool.

After twenty-four hours, the adults are removed and the leaf discs bearing eggs are then dipped in acetone solution of the compound being tested at 0.1%.

After submersion for one second, the solvent on the leaf discs is allowed to dry and the leaf discs are then glued with the underside to a plastic petri dish to prevent crumpling.

Six days later (when all the eggs on untreated discs have emerged) , the number of unhatched eggs is calculated as a percentage of the total number originally present, which value is corrected for any spontaneous non-emergence observed in control discs treated only with solvent by employment of the Abbott formula, W.S. Abbott, Jour. Econ. Entomol. 18 265-7 (1925).

The results of this testing are tabulated below: Compound No . % Eggs Unhatched 5 100 13 100 27 100 28 100 30 100 31 100 44 100 A wettable powder suitable for field application after dilution can be formulated by blending and then air-milling a mixture of 20 to 30% of an ester or thioester of this invention, 60 to 70% of a solid carrier such as Attaclay X-250, 1 to 3% of an anionic surfactant, such as Igepon T-77, and 3 to 5% of a dispersing agent such as Marasperse N-22.

The wettable powder is applied, after dilution with water, using ultra-low volume sprayers. Dilutions containing the ester within a concentration range of about 0.005% to 1% are generally employed.

The compounds can be formulated as a 25% active ingredient dust having the following composition: Active Substance 25% Synthetic Calcium Silicate 5% Attapulgite Clay 68.5% Dust Inhibitor and Sticker 1.5%

Claims (1)

1. 44345/3 CLAIMSt 1. A compound of formula A, B or C 0 wherein X is -0- or -S-; R is alkyl of ten to twenty-two carbon atoms, alkenyl of ten to twenty-two carbon atoms or alkynyl of ten to twenty-two carbon atoms; R' is alkylene of one to six carbon atoms; A is alkylene of up to twenty carbon atoms, alkenylene of two to twenty carbtm atoms, alkynylene of two to twenty carbon atoms, cycloalkylene having from four to six carbon atoms in the ring, or arylene of six to twenty carbon atoms; A' is cycloalkylene having from four to six carbon atoms in the ring, or arylene of six to twenty carbon atoms optionally substituted by one or two alkyl, halogen or nitro groups; n is zero or a positive integer from one to four; and p is zero or one; with the proviso that when A' is 1,4-phenylene, p is one* - 12 - 44345/5 2. A compound of formula A according to claim 1 wherein R is alkyl, alkenyl or alkynyl as defined in claim 1 and n is zero. 3. A compound according to claim 2 wherein X is -0-. 4. The compound hexadecyl cyclopropanecarboxyiate. 5. A compound of formula B according to claim 1 wherein n is zero and A is alk lene* 6· The compound 1 ,10-decylene bis(cyclopropanecarboxyiate). 7. A compound according to claim 1 of formula 0 wherein A is alkylene, alkenylene or alkynylene, R is an alkyl, alkenyl, alkynyl, or cycloalkyl group of at least ten carbon atoms and X is -0- or -S-. 8* A compound of formula A or formula B of claim 1 wherein n is one, two, three or four, p is zero, and A, R and X are- as defined in claim 1. 9. A compound of formula A according to claim 1 or claim 8 wherein R is alkyl, alkenyl, or alkynyl and n is one to four* 10. A compound according to claim 9 wherein X is -0- and n is two. 11. The compound tetradecyl 3-cyclopropanepropionate. = 1 2. A compound of formula B according to claim 1 or claim 8 wherein n is two and A is alkylene, cycloalkylene or arylene. 13· A compound according to claim 1 2 wherein A is cyclo-hexylene or p-phenylene. 1 . A compound of formula B according to claim 1 wherein A is 1 ,3-cyclobutylene, 1 , 3-cyclopentylene, or 1 ,4-cyclohexylenet 1 5. A compound according to claim 14 wherein n is zero or two. /of formula B' 1 6. The compound; according to claim 1 wherein n is zero, X ID -O^, p is one, R' is methylene and A is 1 ,4-cyclohexylene. 1 7. A compound of formula B or formula C of claim 1 , wherein R' is -CHg- , and A and A1 are arylene with the proviso that when A* is 1 ,4-phenylene, p is one. 18. A compound according to formula B of claim 1 of formula wherein A is an arylene group and the C-0-CH_- 2 substituents are in a para relationship. 1 9. A compound of formula B according to claim 1 or claim 1 7 wherein A is arylene, n is zero, p is one and R' is methylene. phenylenedimethyl 20. The compound 1 ,4-dlmoiihylonophonyl bis(cyclppropanecarboxylate). 14 - 44345/3 21. The compound p-phenylene bis(cyclopropanecarboxylate). 22. A compound of formula C according to claim 1 or claim 17 wherein R' is methylene when p is one and A' is 1 ,4-phenylene, 2 i5-dimethyl-1 ,4-phenylene, 41 »4*-biphenylene, 2,5-dichloro- 1.4-phenylene, or 2-nitrc—1 ,4-phenylene. 23. A compound of formula C according to claim 1 wherein p is aero and A' is 2,5-dimeth 1-1 ,4-phenylene, 4' »4'-biphenylene, 2.5-dichloro-1 ,4-phenylene or 2-nitro-1 ,4-phenylene. 24» A compound of formula C of claim 1 wherein A' is cycloalkylene of four to six carbon atoms, and R and p are as defined in claim 1* 25. A compound of formula C according to claim 1 or claim 24 wherein R» is methylene, ethylene, trimethylene or tetramethylene. 26. A compound according to formula B or formula C according to any one of claims 1, 14, 24 or 25 wherein A or A' is cyclobutylene, cyclopentylene or cyclohexylene. 27. The compound bis(cyclopropanemethyl) cyclohexane-1 ,4-dicarboxylate. 28. The compound c cctadecyl cyclopropanecarboxylate. 29. The compound tetradecyl cyclopropanecarboxylate. 30. The compound octadec-9-enyl cyclopropanecarboxylate., 31. The compound 1 , 12-dodecylene bis(cyclopropenecarboxylate). 32.. A compound of formula B according to claim 1 wherein n is 2, A is 1 ,4-phenylene, R' is methylene and p is one. - 15 - 44345/2 33. Compounds of formula A, B and C substantially as herein ψ described and exemplified. 34. A process for preparing a compound according to any one of claims 1-33 which comprises any of the syntheses substantially as described and exemplified herein. 35. Composition for the control of mites which comprises an agriculturally inert carrier and at least one compound according to any of claims 1-33. 36. Composition for the control of mites substantially as described and exemplified. 37. Method of controlling mites which comprises contacting said mites with a pesticidally effective amount of a compound according to any of claims 1-33. 38. Method for the control of mites substantially as described and exemplified.