Claims
- 1. A compound of the formula ##STR13## in which Ar is a phenyl or thieynl group which may be substituted by (C.sub.1-6)alkyl, halo, (C.sub.1-4)haloalkyl, (C.sub.1-4)alkoxy, (C.sub.1-4)haloalkoxy, or by a substituent having the structure --A--(CR.sup.1 R.sup.2)--A-- where R.sup.1 and R.sup.2 are independently hydrogen, halogen, or (C.sub.1-2)alkyl, n is 1 or 2, and each A is O or CH.sub.2 and is bonded to an adjacent carbon atom of the aromatic ring; Z is oxygen, sulfur, or methylene; and Ar' is phenoxylphenyl, 2-methyl[1,1'-biphenyl]-3-yl, or 6-phenoxy-2-pyridyl each optionally substituted with halo or lower alkyl.
- 2. A compound of claim 1 in which Ar' is 3-phenoxyphenyl, 4-fluoro-3-phenoxyphenyl, 2-methyl[1,1'-biphenyl]-3-yl, or 6-phenoxy-2-pyridyl.
- 3. A compound of claim 2 in which Ar is selected from phenyl, (C.sub.1-6)alkylphenyl, halophenyl, (C.sub.1-4)haloalkylphenyl, (C.sub.1-4)alkoxyphenyl, (C.sub.1-4)haloalkoxyphenyl, and 1,3-benzodioxol-5-yl.
- 4. A compound of claim 3 in which Ar' is 3-phenoxyphenyl; Z is oxygen; and Ar is selected from phenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-t-butylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-(2-fluoroethoxy)phenyl, 4-difluoromethoxyphenyl, 4-trifluoromethoxyphenyl and 1,3-benzodioxol-5-yl.
- 5. A compound of claim 4 in which Ar is 4-chlorophenyl for which [.alpha.].sub.D.sup.25 in chloroform is negative.
- 6. A compound of claim 4 in which Ar is 4-trifluoromethylphenyl.
- 7. A compound of claim 4 in which Ar is 4-trifluoromethylphenyl.
- 8. A compound of claim 3 in which Ar' is 4-fluoro-3-phenoxyphenyl; Z is oxygen; and Ar is selected from 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-t-butylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-ethoxylphenyl, 4-(2-fluoroethoxy)phenyl, 4-difluoromethoxyphenyl, 4-trifluoromethoxyphenyl, and 1,3-benzodioxol-5-yl.
- 9. A compound of claim 8 in which Ar is 4-chlorophenyl.
- 10. A compound of claim 9 for which [.alpha.].sub.D.sup.25 in chloroform is negative.
- 11. A compound of claim 8 in which Ar is 4-trifluoromethylphenyl.
- 12. A compound of claim 8 in which Ar is 4-ethoxyphenyl.
- 13. A compound of claim 8 in which Ar is 4-trifluoromethoxyphenyl.
- 14. A compound of claim 3 in which Ar, is 2-methyl[1,1,'-biphenyl]-3-yl; Z is oxygen; and Ar is selected from phenyl, 4-fluorophenyl, 3chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-t-butylphenyl, 4-trifluoromethylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-(2-fluoroethoxy)phenyl, 4-difluoromethoxyphenyl, 4-trifluoromethoxyphenyl, and 1,3-benzodioxol-5-yl.
- 15. A compound of claim 14 in which Ar is 4-trifluoromethoxyphenyl.
- 16. A compund of claim 3 in which Ar is 4-chlorophenyl; Z is sulfur; and Ar' is selected from 3-phenoxyphenyl, 4-fluoro-3-phenoxyphenyl, and 2-methyl[1,1'-biphenyl]-3-yl.
- 17. A compound of claim 16 in which Ar' is 4-fluoro-3-phenoxyphenyl.
- 18. A compound of claim 3 in which Ar' is 6-phenoxy-2-pyridyl, Z is oxygen, and Ar is 4-chlorophenyl.
- 19. A compound of claim 3 in which Ar' is selected from 3-phenoxyphenyl, 4-fluoro-3-phenoxyphenyl, and 2-methyl[1,1'-biphenyl]-3-yl; Z is methylene; and Ar is selected from 3-chlorophenyl, 4-chlorophenyl,4-methylphenyl, 4-ethoxyphenyl, and 4trifluoromethoxyphenyl.
- 20. A compound of claim 19 in which Ar' is 3-phenoxyphenyl and Ar is 4-chlorophenyl.
- 21. A compound of claim 19 in which Ar' is 3-phenoxyphenyl and Ar is 4-trifluoromethylphenyl.
- 22. A compound of claim 19 in which Ar' is 4-fluoro-3-phenoxyphenyl and Ar is 4-chlorophenyl.
- 23. A compound of claim 19 in which Ar' is 4-fluoro-3-phenoxyphenyl and Ar is 4-trifluoromethylphenyl.
- 24. A compound of claim 19 in which Ar' is 4-fluoro-3-phenoxyphenyl and Ar is 4-trifluoromethoxyphenyl.
- 25. A compound of claim 19 in which Ar' is 2-methyl[1,1'-biphenyl]-3-yl and Ar is 4-trifluoromethylphenyl.
- 26. A compound of the formula ##STR14## in which Ar is a pheny or thienyl group which may be substituted by (C.sub.1-6)alkyl, halo, (C.sub.1-4)haloalkyl, (C.sub.1-4)alkoxy, (C.sub.1-4)haloalkoxy, or by a substituent having the structure --A--(CR.sup.1 R.sup.2)--A-- where R.sup.1 and R.sup.2 are independently hydrogen, halogen, or (C.sub.1-2)alkyl, n is 1 or 2, and each A is O or CH.sub.2 and is bonded to an adjacent carbon atom of the aromatic ring; and Ar' is a phenoxyphenyl, 2-methyl[1,1,'-biphenyl]-3-yl, or 6-phenoxy-2-pyridyl each optionally substituted with halo or lower alkyl.
- 27. A compound of claim 26 in which Ar' is selected from 3-phenoxyphenyl and 4-fluoro-3-phenoxyphenyl and Ar is selected from 4-chlorophenyl, 4-bromophenyl, and 4-methoxyphenyl.
- 28. A compound of claim 27 in which Ar' is 4-fluoro-3-phenoxyphenyl and Ar is 4-chlorophenyl.
- 29. A compound of the formula ##STR15## in which Ar is a phenyl or thienyl group which may be substituted by (C.sub.1-6)alkyl, halo, (C.sub.1-4)haloalkyl, (C.sub.1-4)alkoxy, (C.sub.1-4)haloalkoxy, or by a substituent having the structure --A--(CR.sup.1 R.sup.2)--A-- where R.sup.1 and R.sup.2 are independently hydrogen, halogen, or (C.sub.1-2)alkyl, n is 1 or 2, and each A is O or CH.sub.2 and is bonded to an adjacent carbon atom of the aromatic ring; and Ar' is phenoxyphenyl, 2-methyl[1,1'-biphenyl]-3-yl, or 6-phenoxy-2-pyridyl each optionally substituted with halo or lower alkyl.
- 30. A compound of claim 29 in which Ar' is selected from 3-phenoxyphenyl, 4-fluoro-3-phenoxyphenyl, and 2-methyl[1,1'-biphenyl]-3 -yl and Ar is selected from 4-chlorophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, and 4-ethoxyphenyl.
- 31. An insecticidal or acaricidal composition comprising an insecticidally or acaricidally effective amount of a compound of claim 2 in admixture with one or more compatible agriculatural carriers, diluents, adjuvants, or complementary pesticides.
- 32. An insecticidal composition comprising an insecticidally effective amount of a compound of claim 26 in admixture with one or more compatible agricultural carriers, diluents, adjuvants, or complementary pesticides.
- 33. An insecticidal composition comprising an insecticidally effective amount of a compound of claim 27 in admixture with one or more compatible agriculatural carriers, diluents, adjuvants, or complementary pesticides.
- 34. A method of controlling insects and acarids by applying to the locus where control is desired an insecticidally or acaricidally effective amount of a compound of claim 1.
- 35. A method of controlling insects by applying to the locus where control is desired an insecticidally effective amount of a compound of claim 26.
- 36. A method of controlling insects by applying to the locus where control is desired an insecticidally effective amount of a compound of claim 29.
BACKGROUND OF THE INVENTION
This application is a continuation-in-part of application Ser. No. 041,551, filed Apr. 23, 1987 abandoned.
This invention relates to novel pyrethroid-like insecticides which effectively control infestations of undesirable insects and acarids and simultaneously display remarkably low toxicity to fish. Synthetic pyrethroids have been the focus of intensive research activity for more than a decade. The pioneering work of Elliott, as described in U.S. Pat. No. 4,024,163, established that synthetic pyrethroids could be synthesized with sufficient stability to light to be commercially attractive. The vast majority of these new pyrethroids are esters of substituted cyclopropanecarboxylic acids similar to those described by Elliott. Initially, compounds having the aforementioned structure were thought to be required for insecticidal activity; however, considerable effort has been successfully directed toward defining compounds which are nominally described as pyrethroids based upon similarities in molecular geometry and insecticidal activity. In some of these compounds only the ester linkage has been retained; in others the substituted cyclopropane ring has been retained; and in yet others neither the substituted cyclopropane ring nor the ester linkage has been retained. In the current invention an unsubstituted cyclopropane group is incorporated into pyrethroidlike compounds. These novel compounds lack the substituted cyclopropanecarboxylic acid moiety typical of the compounds described by Elliott and those who followed him. Further, these compounds display pyrethroid-like insecticidal activity while possessing remarkably low toxicity to fish in comparison with the notorious toxicity to fish exhibited by cyclopropanecarboxylates.
U.S. Pat. No. 4,397,864 discloses a class of pyrethroid-like compounds hving the following subgeneric formula: ##STR2## wherein Ar is optionally substituted phenyl, optionally substituted naphthyl, or 1,3-benzodioxol-5-yl;
U.S. Pat. No. 4,073,812 covers a closely related series of compounds having the generic formula: ##STR3## wherein R is halogen, lower alkyl, or lower alkoxy;
U.S. Pat. No. 4,562,213 covers another similar series of compounds of the formula: ##STR4## wherein R.sup.1 is hydrogen, halogen, or methyl;
United Kingdom patent application GB No. 2 120 664A discloses a class of aromatic-substituted alkane derivatives having the following generic formula: ##STR5## wherein Ar stands for a substituted or unsubstituted phenyl or naphthyl group;
Belgian patent No. 902147 discloses a class of compounds having the following generic formula: ##STR6## wherein Ar represents a substituted or unsubstituted phenyl or naphthyl group;
The compounds of this invention may be described as 2-(optionally substituted aryl)-2-cyclopropylethyl substituted-benzyl ethers and thioethers and 1-(optionally substituted aryl)-1-cyclopropyl-4-(substituted aryl)butanes. These compounds contain an asymmetric carbon atom; the invention thus includes individual stereoisomers as well as racemic and non-racemic mixtures of enantiomers of the instant compounds.
This invention also encompasses insecticidal compositions containing the pyrethroid ethers, thioethers, and butanes and their use for controlling insects. The compounds of this invention are effective for control of a wide variety of insects and acarids and may be expected to be useful in any situation for which pyrethroid insecticides are indicated. The compounds of this invention find particular utility in applications where there is a possibility of significant contamination of streams, rivers, and lakes by insecticidal material. Their low toxicity to fish will obviate concern about potential ecological problems associated with the use of pyrethroids in environments where such contamination is possible.
The 2-(optionally substituted aryl)-2-cyclopropylethyl substituted-benzyl ethers, thioethers, and the 1- (optionally substituted aryl)-1-cyclopropyl-4-(substituted aryl)butanes have the general formula: ##STR7## in which Ar is a substituted or unsubstituted phenyl, naphthyl, or thienyl. A substituted Ar may have one or two, not necessarily identical, substituents. Preferably Ar is phenyl and is monosubstituted at the 4-position. Preferred substituents include, but are not limited to, (C.sub.1-6)alkyl, halo, (C.sub.1-4)haloalkyl, (C.sub.1-4)alkxoy, (C.sub.1-4)haloalkoxy. Halo includes fluoro, chloro, and bromo. The term alkyl includes straight and branched chain alkyl groups having 1-6 carbon atoms, preferably 1-4 carbon atoms. The terms haloalkyl and haloalkoxy include alkyl and alkoxy groups in which one or more hydrogen atoms have been replaced by fluorine, chlorine, or bromine atoms including all combinations thereof. Further, the substituent may have the structure --A--(CR.sup.1 R.sup.2)n--A-- where R.sup.1 and R.sup.2 are independently, hydrogen, halogen, or (C.sub.1-2)alkyl, n is 1 or 2, and each A, which may be O, S, or CH.sub.2, is bonded to a carbon atom of the aromatic ring, the carbons to which the A groups are attached being adjacent to each other in the ring. Illustrative of this mode of substitution are compounds in which Ar is 1,3-benzodioxolyl, 2,2-difluoro-1,3-benzodioxolyl, or 2,3-dihydro-2,2-dimethylbenzofuranyl. Typical Ar groups include:
The ether and thioether compounds of this invention are prepared by reacting an appropriate 2,2-disubstituted ethanol or thioethanol with sodium hydride, thus preparing the corresponding sodium ethoxide. The ethoxide or thioethoxide can, in turn, be reacted with an appropriately substituted benzyl halide to prepare the insecticidal ether or thioether. Example 1 describes the reaction of 2-cyclopropyl-2-(4-chlorophenyl)ethanol with sodium hydride in tetrahydrofuran and the reaction of the resulting sodium salt with (4-fluoro-3-phenoxyphenyl)methyl chloride to prepare (4-fluoro-3-phenoxyphenyl)methyl 2-cyclopropyl-2-(4-chlorophenyl)ethyl ether, Compound 16 of Table 1.
Numerous references describe the preparation of the substituted halides or preparation of the corresponding alcohols from which the halides may be prepared by conventional methods. The halides may be selected from chlorides, bromides, or iodides. Other leaving groups that may be readily displaced by a substituted ethoxide or thioethoxide may be substituted for the halogen atom of the benzyl halide. Examples of such leaving groups include, but are not limited to, methanesulfonate, trifluoromethanesulfonate, and p-toluenesulfonate.
The alcohol intermediates may be prepared from the aryl cyclopropyl ketones by conventional methods. In Example 1 the 4-chlorophenyl cyclopropyl ketone is reacted with sodium hydride and methyl triphenylphosphonium bromide to prepare 1-(4-chlorophenyl)-1-cyclopropylethene. Hydroboration of this olefin with bis(3-methyl-2-butyl)borane, followed by treatment with aqueous sodium hydroxide and hydrogen peroxide completes the synthesis of the ethanol from which the ether may be prepared as described above.
The substituted ethanol may be converted to the corresponding ethanethiol by reacting triphenylphosphine with diisopropyl azodicarboxylate and then reacting the resulting intermediate with the substituted ethanol. Quenching this reaction with thiolacetic acid produces the thiolacetate. Reduction of the thiolacetate produces the substituted thiol from which the thioether can be prepared by the same method described above for the ethers. Example 2 details the synthesis of (4-fluoro-3-phenoxy)methyl 2-cyclopropyl-2-(4-chlorophenyl)ethyl thioether, Compound 21 of Table 1 by this method.
Separation of the optical isomers can be effected by first preparing the 2,2-disubstituted acetic acid. One method for this preparation is to react the aryl cyclopropyl ketone with the anion prepared from 2-trimethylsilyl-1,3-dithiane and n-butyllithium. The resulting 2-[(aryl)cyclopropylmethylene]-1,3-dithiane may then be reacted with mercury (II) chloride, water, and methanol, producing methyl 2-aryl-2-cyclopropylacetate. Hydrolysis of the acetate to the acid and preparation of the acid chloride may be followed by reaction with (S)-4-(1-methylethyl)-2-oxazolidinone, previously prepared by reacting (S)-2-amino-3-methyl-1-butanol with phosgene. The two diastereomers of N-(2-aryl-2-cyclopropylacetyl)-4-(1-methylethyl)-2-oxazolidinone may then be separated chromatographically. Reduction of the individual diastereomers of the oxazolidinone with lithium aluminum hydride produces the (S) or (R)-2-aryl-2-cyclopropylethanols, each substantially free of the other antipode. In Example 3 details are provided for this method of preparing the two stereoisomers of (4-fluoro-3-phenoxyphenyl)methyl 2-cyclopropyl-2-(4-chlorophenyl)ethyl ether, Compounds 17 and 18 of Table 1.
The saturated, hydrocarbon compounds of this invention are prepared by reacting a substituted-phenyl cyclopropyl ketone with vinylmagnesium bromide to prepare the corresponding 1-(substituted phenyl)-1-cyclopropyl-2-propen-1-ol. Oxidation of this unsaturated alcohol yields 3-(substituted phenyl)-3-cyclopropylpropenal. The reaction of triphenylphosphine and a substituted-benzyl bromide yields the corresponding substituted benzyltriphenylphosphonium bromide which, in turn, can be reacted with the 3-(substituted phenyl)-3-cyclopropylpropenal in the presence of n-butyllithium to yield a 1-(substituted phenyl)-1-cyclopropyl-4-(substituted phenyl)butadiene. Hydrogenation of this butadiene produces the saturated insecticidal compounds of Formula I. Example 4 details the synthesis of 1-(4-chlorophenyl)-1-cyclopropyl-4-(3-phenoxyphenyl)butane, Compound 88 of Table 1, by this method.
Alternatively, the saturated, hydrocarbon compounds may be synthesized by reacting an appropriately substituted benzaldehyde with ethoxycarbonylmethylenetriphenylphosphorane, producing the corresponding ethyl 3-(substituted aryl)acrylate. Reduction of this ester with lithium aluminum hydride yields the corresponding 3-(substituted aryl)propanol. Reaction of this alcohol with phosphorous tribromide yields the propyl bromide which, in turn, is reacted with triphenylphosphine, producing the corresponding 3-(substituted aryl)propyltriphenylphosphonium bromide. The intermediate 1-(substituted phenyl)-1-cyclopropyl-4-(substituted aryl)-1-butene is prepared by reaction of the phosphonium bromide with the appropriate substituted-phenyl cyclopropyl ketone in the presence of n-butyllithium. Catalytic hydrogenation with Raney nickel completes the synthesis. By this method 1-(4-chlorophenyl)-1-cyclopropyl-4-(3-phenoxyphenyl)butane, Compound 88 of Table 1, was synthesized as described in Example 7.
Certain substituted-phenyl cyclopropyl ketones, e.g., 4-chlorophenyl cyclopropyl ketone, are commercially available. Others can be synthesized by starting with an appropriately substituted benzoic acid which can be converted to the acid chloride by the usual methods, e.g., by reaction with oxalyl chloride. Reaction of the acid chloride with N-methoxy-N-methylamine hydrochloride yields the corresponding substituted N-methoxy-N-methylbenzamide. The desired substitutedphenyl cyclopropyl ketone is then obtained by reacting the benzamide with cyclopropylmagnesium bromide. Example 5, Steps A-C, representative of this method, provide details for the synthesis of cyclopropyl (4trifluoromethylphenyl) ketone.
Alternatively, the substituted-phenyl cyclopropyl ketones may be prepared by reacting cyclopropanecarboxylic acid chloride with an appropriately substituted-phenyl compound in the presence of a Friedel-Crafts catalyst, e.g., aluminum chloride. In Example 6, Step A, cyclopropanecarboxylic acid chloride is reacted with ethoxybenzene in the presence of aluminum chloride, yielding cyclopropyl (4-ethoxyphenyl) ketone.
The intermediate butadienes of the formula: ##STR8## Ar and Ar' are defined as above are themselves insecticidal and acaricidal. Table 2 lists these compounds.
Also, the intermediate butenes of the formula: ##STR9## wherein Ar and Ar' are defined as above are insecticidal and acaricidal. Table 3 lists these compounds. These olefins may exist in two configurations, the E and Z isomers. In the E isomer the cyclopropyl group and the --CH.sub.2 CH.sub.2 Ar' moiety are in a cis configuration in relation to the double bond and in the Z isomer these same moieties are situated in a trans configuration. In one instance an example of a Z isomer, Compound B13, was separated by rotating disk thin layer chromatography from a mixture of E and Z isomers. This enriched the residue, Compound B12, in the E isomer relative to the Z isomer. Comparisons of the insecticidal data for these compounds indicate that E isomers are significantly more active than the Z isomers.
The following examples provide additional details of the synthetic methods used to prepare the insecticidal ethers, thioethers, and hydrocarbons of this invention. Tables 1, 2, and 3 list these compounds. The compound numbers shown in each example are those assigned in these tables.
US Referenced Citations (3)
| Number |
Name |
Date |
Kind |
| 4153731 |
Karrer |
May 1979 |
|
| 4575517 |
Knger et al. |
Mar 1986 |
|
| 4611004 |
Ackermann et al. |
Sep 1986 |
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| 118534 |
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JPX |
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| 132901 |
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Continuation in Parts (1)
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Number |
Date |
Country |
| Parent |
041551 |
Sep 1987 |
|
Patent Grant
4808762
