INSECTICIDAL N-(SUBSTITUTED ARYLMETHYL)-4-[BIS(SUBSTITUTED PHENYL)METHYL]PIPERIDINES

Abstract: Compounds of structure (I), the corresponding N-oxides and agriculturally acceptable salts, are disclosed as effective insecticides, in which Q is selected from hydrogen, hydroxy, and fluorine; R is selected from a heteroaryl having 5 or 6 ring atoms, and (II) in which V is hydrogen, halogen, alkyl, haloalkyl, or alkoxy; W and X are independently selected from a wide variety of substituents, Y and Z are independently selected from hydrogen and alkoxy; W and X taken together may be -OCH2CH2O-, -CH2C(CH3)2O-, or -OC(CH3)2O-; R<1> and R<2> are independently selected from phenyl substituted with halogen, alkyl, haloalkyl, haloalkoxy, alkylsulfonyloxy, and haloalkylsulfonyloxy; and n is 1, 2 or 3; with the proviso that each aliphatic moiety contains not more than 6 carbon atoms, halogen means chlorine or fluorine, and each alkyl substituent on an amino nitrogen contains 1 to 3 carbon atoms. The manner of preparing these compounds is also disclosed.

Description: INSECTICIDAL N-(SUBSTITUTED ARYLMETHYL)-4- [BIS(SUBSTITUTED PHENYL)METHYL]PIPERIDINES The present invention relates to methods for controlling insects. In particular, it relates to control by the application of certain N-(substituted aryimethyl)-4-[bis(substituted phenyl)methyl]piperidines to the locus where insect control is needed. While not all compounds of the class are novel, the insecticidal efficacy of these compounds is heretofore unknown. Many derivatives of N-(substituted arylmethyl)-4-[bis(substituted) phenylmethyl]piperidines have been disclosed as cardiovascular or antiallergy agents. South African Pat. No.8604-552A discloses such use for compounds of the formula: in which p is 0, 1 , or 2; A is, inter alia, hydrogen or hydroxy; m is 0 to 6 inclusive; Q is -CH-, -CH 2 -, or -CH(OH)-; d and n are 0 or 1 , and the dotted lines represent double bonds consistent with the valence of carbon; Ar, D, and R are selected, inter alia, from X, Y, and Z are selected from a variety of substituents, including hydrogen, lower alkyl, halogen, nitro, cyano, amino, alkoxy, thioalkyl, and carbonyl- or sulfonyl-containing groups; B is, inter alia, sulfur or oxygen. There are several provisos, and the pharmaceutically acceptable salts of these compounds are also disclosed as having the same utility. U.S. Pat. No. 4,628,095 dicloses as cardiovascular agents compounds of the formula in which Ar is phenyl, optionally substituted with halogen; R is lower alkoxy or di(lower alkyl)amino; R-| is hydrogen, lower alkoxycarbonyl, carboxy, or lower alkyl aminocarbonyl; and n is 0 or 1 , provided that when R-| hydrogen, n is 1. It has now been found that compounds of the following structure and their corresponding N-oxides, as well as their agriculturally acceptable salts, are active as insecticides: in which Q is selected from hydrogen, hydroxy, and fluorine; R is selected from a heteroaryl having 5 or 6 ring atoms, and in which V is hydrogen, halogen, alkyl, haloalkyl, or alkoxy; W is hydrogen, halogen, alkyl, haloalkyl, alkoxy; phenoxy, or phenylalkoxy; X is hydrogen, hydroxy, halogen, alkyl, alkoxyalkyl, alkoxy, cycloalkyl- alkoxy, haloalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, alkylsilyloxy, alkylthio, haloalkylthio, cyano, cyanoalkoxy, nitro, amino, monoalkylamino, dialkylamino, alkylaminoalkoxy, alkylcarbonylamino, alkylcarbonyl, alkoxycarbonylamino, alkoxycarbonyl, alkylaminocarbonyl, aminocarbonyloxy, phenyl, phenylalkoxy, phenoxy, or phenoxyalkyi, each phenyl ring optionally substituted with halogen, alkoxy, or haloalkoxy; Y and Z are independently selected from hydrogen and alkoxy; W and X taken together may be -OCH2CH2O-, -CH2C(CH3)2θ-, or -OC(CH 3 )2θ-; R 1 and R 2 are independently selected from phenyl substituted with halogen, alkyl, haloalkyl, haloalkoxy, alkylsulfonyloxy, and haloalkylsulfon¬ yloxy; and n is 1 , 2, or 3; with the proviso that each aliphatic moiety contains not more than 6 carbon atoms, halogen means chlorine or fluorine, and each alkyl substituent on an amino nitrogen contains 1 to 3 carbon atoms. Preferred are those compounds in which R is in which V is selected from hydrogen and halogen; Y and Z are each hydrogen; W is selected from hydrogen, halogen, and alkoxy; and X is selected from hydrogen, hydroxy, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, alkylthio, halo¬ alkylthio, monoalkylamino, dialkylamino, alkoxyalkyl, alkoxyalkoxy, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, alkylcarbonylamino, aminocarbonyloxy, alkoxycarbonylamino, cyano, phenyl, phenoxy, phenoxyalkyi, and optionally substituted phenylalkoxy; W and X taken together may be -OCH2CH2O-, -CH2C(CH3)2θ-, or -OC(CH 3 )2θ-; R 1 and R 2 are independently selected from phenyl substituted with halogen or haloalkoxy; and n is 1 , 2, or 3, with the proviso that one of R 1 and R 2 is phenyl substituted in the para position, as well as their N-oxides and salts. Particularly preferred are those compounds in which V is selected from hydrogen and fluorine; Y and Z are each hydrogen; W is selected from hydrogen, halogen, methoxy and ethoxy ; and X is selected from hydrogen, halogen, methyl, methoxy, ethoxy, n- propoxy, n-butoxy, perfluoroethoxy, perfluoroethylthio, cyano, phenyl, phenoxy, phenylmethoxy, dimethylamino, ethoxymethyl, ethylcarbonyl, ethoxycarbonyl, allyloxy, propargyloxy, 2-methylpropoxy, cyclopropyl- methoxy, 2-chloro-2-propenoxy, 2-methyl-2-propenoxy, 3-methyl-2- butenoxy, cyanomethoxy, 2-butynoxy, and ethylcarbonylamino; W and X taken together may be -CH2C(CH3)2θ-; n is 1 ; and R 1 and R 2 are each p-trifluoromethoxyphenyl, and each aliphatic moiety contains no more than 5 carbons, as well as their N-oxides and salts. The compounds of the present invention were prepared by methods generally known to those skilled in the art. In the method shown in Schema 1 , where R 1 and R 2 are the same, ethyl piperidin-4-ylcarboxylate was reacted with either an appropriately substituted alkyl halide, for example, 4- methoxyphenylmethyl bromide, or with an appropriately substituted aldehyde, for example, 4-phenoxybenzaldehyde, affording the corresponding ethyl N-substituted alkylpiperidin-4-ylcarboxylate (A). Intermediate (A) was then treated with more than two molar equivalents of the Grignard reagent of an appropriately substituted halide, for example, 4- trifluoromethoxyphenyl magnesium bromide, yielding the desired N- 5 - (substituted alkyl)-4-[bis(substituted)hydroxymethyl]piperidine (I), for example, N-(4-methoxyphenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)- hydroxymethyl]piperidine (Compound 24). Examples 1-3, 5, 6, and 10 provide detailed descriptions of how these reactions are conducted. Another method, shown in Schema 2, again for cases where R 1 and R 2 are the same, uses the method of D.A. Walsh et al. (J. Med. Chem. 1989, 32, 105-118). In this method ethyl piperidin-4-ylcarboxylate was reacted with diethyl carbamoyl chloride, under basic conditions, affording the corresponding intermediate, ethyl N-diethylaminocarbonylpiperidin-4-yl- carboxylate (B). Intermediate (B) was treated with more than two molar equivalents of the Grignard reagent of an appropriately substituted halide, yielding the corresponding N-diethylaminocarbonyl-4-[bis(substituted)- hydroxymethyl]piperidine (C). Intermediate (C) was then treated with lithium aluminum hydride, affording the 4-[bis(substituted)hydroxymethyl]piperidine (li), for example, 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. As depicted in Schema 2C, intermediate (ϋ) was reacted with either an appropriately substituted alkyl halide or with an appropriately substituted aldehyde, as previously described, affording the desired N-(substituted alkyl)-4-[bis(substituted)hydroxymethyl]piperidine (I), for example, N-(4- ethoxycarbonylphenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxy- methyl]piperidine (Compound 57). Example 7 provides a detailed description of how this reaction is conducted. The preparation of intermediate (N) using the method described above provided relatively low yields of (N). To obtain improved yields of (H), two other synthesis routes to this intermediate were used. In the first alternative route to intermediate (N), shown in Schema 2A, the hydrochloride salt (D) of an N-phenylmethyl-4-[bis(substituted)hydroxy- methyl]piperidine (I), for example, N-phenylmethyl-4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]piperidine, was treated with ammonium formate in the presence of 10% palladium on charcoal, readily affording intermediate (li). Again, intermediate (H) was reacted as shown in Schema 2C, affording the desired N-(substituted alkyl)-4-[bis(substituted)hydroxymethyl]piperidine (i), for example, N-[4-(methylcarbonylamino)phenylmethyl]-4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine (Compound 66). Example 12 provides a detailed description of how this reaction is conducted. In the second alternative route to intermediate (N), shown in Schema 2B, ethyl pyridin-4-ylcarboxylate was reacted with more than two molar equivalents of the Grignard reagent of an appropriately substituted halide, affording the corresponding 4-[bis(substituted)hydroxymethyl]pyridine (E). The hydrochloride salt (F) of intermediate (E) was then prepared and was hydrogenated in the presence of platinum oxide, affording the correspon¬ ding 4-[bis(substituted)hydroxymethyl]piperidine hydrochloride salt (MA). As shown in Schema 2C, intermediate (MA) was in turn reacted under basic conditions, affording the desired N-(substituted alkyl)-4-[bis(substituted)- hydroxymethyl]piperidine (i), for example, N-[4-(2-propyn-1 -yloxy)phenyl- methyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine (Compound 65). Example 11 provides a detailed description of how this reaction is conducted. The intermediate 4-[bis(substituted)hydroxymethyl]piperidine (ϋ) described above, was also reacted, as shown in Schema 2C, with an appropriately substituted acid chloride, for example, 3-chloro-4-methoxy- benzoyl chloride, under basic conditions, yielding the corresponding N- (substituted carbonyl)-4-[bis-(substituted)hydroxymethyl]piperidine (G). Intermediate (G) was reduced with borane-methyl sulfide complex, affording the desired N-(substituted alkyl)-4-[bis(substituted)hydroxymethyl]piperidine (i), for example, N-(3-chloro-4-methoxy-phenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine (Compound 44). Example 8 provides a detailed description of how this reaction is conducted. Schema 3 shows the method used when R 1 and R 2 are not the same. Here 4-aminocarbonylpiperidine was reacted with an appropriately substi¬ tuted alkyl halide, for example, 4-propoxyphenylmethyl chloride, under basic conditions, affording the corresponding N -(substituted alkyl)-4-amino- carbonylpiperidine (H). Treatment of intermediate (H) with phosphorous oxychloride yielded the corresponding N-(substituted alkyl)-4-cyano- piperidine (J), which was in turn reacted with the Grignard reagent of an appropriately substituted halide, for example, 4-trifluoromethoxyphenyl- magnesium bromide, yielding the corresponding N-(substituted alkyl)-4- (substituted carbonyl)piperidine (K). Intermediate (K) was reacted with a different Grignard reagent of an appropriately substituted halide, for example, 4-chlorophenylmagnesium bromide, yielding the desired N- (substituted alkyl)-4-[di(substituted)hydroxymethyl]piperidine (i), for example, N-(4-propoxyphenylmethyl)-4-[(4-trifluoromethoxyphenyl)(4- chlorophenyl)hydroxymethyl]piperidine. Example 4 provides a detailed description of how this reaction is conducted. As depicted in Schema 4, the N-(substituted alkyl))-4-[bis(substituted)- hydroxymethyl]piperidines (!) of the present invention may be further reacted by methods known in the art to prepare other nsecticidally active compounds also within the scope of the present invention. In a two-step route, {I}, for example, N-(4-propoxyphenylmethyl)-4- [bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine (prepared in Example 10), was treated with Lawesson's reagent in 1 ,2-dimethoxyethane, affording the corresponding N-(substituted alkyl))-4-[bis(substituted)- mercaptomethyl]piperidine {L). Reduction of (L) with Raney® nickel in the presence of concentrated ammonium hydroxide and 1 ,3-cyclohexadiene in methanol yielded the targeted deshydroxy N-(substituted alkyl))-4-[bis(sub- stituted)methyl]piperidine (IB). Example 13 provides a detailed description of how this reaction is conducted. In an alternate one-step route, the dehydroxylated compounds (IB) were also prepared by the reduction of N-(substituted alkyl))-4- [bis(substituted)hydroxymethyl]piperidines } with trifluoroacetic acid and triethylsilane in methylene chloride. Example 14 provides a detailed description of how this reaction is conducted. The N-(substituted alkyl))-4-[bis(substituted)hydroxymethyl]piperidines 0), for example, N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]piperidine, were also dehydroxylated and fluorinated with diethylaminosulfur trifluoride (DAST) in methylene chloride, affording the corresponding N-(substituted alkyl))-4-[bis(substituted)fluoromethyl]- piperidines (I ). Example 15 provides a detailed description of how this reaction is conducted. Blank Page Blank Page Blank Page Blank Page Blank Page Blank Page Blank Page Included within the scope of the present invention are the N-oxides (IA) of the compounds prepared by methods discussed above. The N-oxides (IA) were prepared by treating these compounds, for example, N-[4-(2- propen-1-yloxy)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxy- methyl]piperidine (Compound 42) with an oxidizing agent, such as 3-chloro- peroxybenzoic acid, yielding the corresponding N-oxide, for example, N-[4- (2-propen-1-yloxy)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxy- methyljpiperidine N-oxide (Compound 43). Example 9 provides a detailed description of how this reaction is conducted. EXAMPLE 1 SYNTHESIS OF N-(4-METHOXYPHENYLMETHYL)-4-[BIS(4-TRI- FLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 24) To a stirred mixture of 1.1 grams (0.045 gram-atom) of magnesium turnings in 30 mL of diethyl ether was added dropwise 15 mL of a solution of 11.0 grams (0.045 mole) of 4-trifluoromethoxyphenyl bromide in 30 mL of diethyl ether. Once the reaction had started, the remaining 15 mL of the bromide solution was added portionwise during a 45 minute period. When the reaction subsided, a solution of 5.0 grams (0.018 mole) of ethyl N-(4- methoxyphenylmethyl)piperidin-4-ylcarboxylate in 20 mL of diethyl ether was added dropwise during a five minute period. Upon completion of addition, the reaction mixture was heated to reflux, where it stirred for about 30 minutes. The reaction mixture was then allowed to cool to ambient temperature, where it stirred for about 18 hours. After this time an aqueous solution saturated with ammonium chloride was added dropwise to quench the reaction. The mixture was then partitioned between water and diethyl ether. The diethyl ether layer was separated and washed first with a solution saturated with sodium chloride and then with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel, with 10% diethyl ether in hexane, 100% diethyl ether, and 10% methanol in diethyl ether as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 6.7 grams of N-(4-methoxyphenylmethyl)-4- [bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine, mp 86-96 °C. The NMR spectrum was consistent with the proposed structure. EXAMPLE 2 SYNTHESIS OF N-(4-PHENOXYPHENYLMETHYL)-4-[BIS(4-TRI- FLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 60) Step A Synthesis of ethyl N-(4-phenoxyphenylmethyl)piperidin-4- ylcarboxylate as an intermediate To a stirred solution of 5.0 grams (0.025 mole) of 4-phenoxybenz- aldehyde and 4.0 grams (0.025 mole) of ethyl piperidin-4-ylcarboxylate in 25 mL of methanol was added 1.6 grams (0.025 mole) of sodium cyanoboro- hydride in one portion. Upon completion of addition, a methanolic solution saturated with hydrogen chloride was added dropwise until the pH of the reaction mixture was about 6.0. The reaction mixture was then stirred at ambient temperature for about 22 hours, after which the pH was again adjusted to about 5.5-6.0 with additional methanolic hydrogen chloride solution. The reaction mixture was poured into 350 mL of aqueous 0.1 M potassium hydroxide solution. The mixture was extracted with three 125 mL portions of diethyl ether, and the combined extracts were washed with one portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concen¬ trated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with 1 :1 ethyl acetate/hexane as the eluant. The product-containing fractions were combined and concentrated, yielding 5.9 grams of ethyl N-(4-phenoxyphenylmethyl)piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of N-(4-phenoxyphenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine (Compound 60) This compound was prepared in a manner analogous to that of Example 1 , with 2.0 grams (0.006 mole) of ethyl N-(4-phenoxyphenyl- methyl)piperidin-4-ylcarboxylate, 7.1 grams (0.029 mole) of 4-trifluorometh- oxyphenyl bromide, and 0.7 gram (0.030 gram-atom) of magnesium turnings in diethyl ether.as the reagents. This reaction differed from Example 1 in that a small amount (10 drops) of 1 ,2-dibromoethane was used to initiate the Grignard reaction. The yield of N-(4-phenoxyphenyl- methyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine was 0.7 gram. The NMR spectrum was consistent with the proposed structure. EXAMPLE 3 SYNTHESIS OF N-[2-(4-METHOXYPHENYL)ETHYL]-4-[BIS(4-TRI- FLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 25) Step A Synthesis of ethyl N-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl- carboxylate as an intermediate The reaction conditions for N-alkylation taught by G.D. Maynard et al., Bioorganic & Medicinal Chemistry Letters, 3(4), pp. 753-756, 1993, were used in the following preparation. A stirred mixture of 5.0 grams (0.032 mole) of ethyl piperidin-4-ylcarboxylate, 5.4 grams (0.032 mole) of 1-(2- chloroethyl)-4-methoxybenzene and 4.4 grams (0.032 mole) of potassium carbonate in 50 mL of dried N,N-dimethylformamide was heated at 70 °C for about 16 hours. After this time the reaction mixture was cooled and partitioned between diethyl ether and water. The organic layer was separated and washed with water and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with mag¬ nesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with diethyl ether/hexane mixtures as eluants. The product- containing fractions were combined and concentrated under reduced pressure, yielding 2.4 grams of ethyl N-[2-(4-methoxyphenyl)ethyl]piperidin- 4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of N-[2-(4-methoxyphenyl)ethyl]-4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine (Compound 25) This compound was prepared in a manner analogous to that of Example 1 , with 1.6 grams (0.005 mole) of ethyl N-[2-(4-methoxyphenyl)- ethyl]piperidin-4-ylcarboxylate, 2.4 grams (0.010 mole) of 4-trifluorometh- oxyphenyl bromide, and 0.3 gram (0.011 gram-atom) of magnesium turnings in about 35 mL of diethyl ether as reagents. This reaction differed from Example 1 in that once the Grignard reaction commenced, the ethyl N- [2-(4-methoxyphenyl)ethyl]piperidin-4-ylcarboxylate was added to the diethyl ether solution of 4-trifluoromethoxyphenyl bromide. The combination was then added dropwise to the reaction mixture, thereby introducing the piperidin-4-ylcarboxylate to the reaction mixture as the Grignard reagent was forming. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. After this time an aqueous solution saturated with ammonium chloride was added dropwise to quench the reaction. The reaction mixture was then extracted with methylene chloride. The combined extracts were washed with a dilute aqueous solution of hydrochloric acid and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with hexane/diethyl ether and ethyl acetate/methanol combinations as eluants. A second column chromatography on silica gel was required, with diethyl ether as the eluant, to afford pure product. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.3 gram of N-[2-(4-methoxyphenyl)ethyl]-4-[bis(4-trifluoromethoxyphenyl)- hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 4 SYNTHESIS OF N-(4-PROPOXYPHENYLMETHYL)-4-[(4- TRIFLUOROMETHOXYPHENYL)(4-CHLOROPHENYL)HYDROXY- METHYLjPIPERIDINE (COMPOUND 7) Step A Synthesis of 4-cyano-N-(4-propoxyphenylmethyl)piperidine as an intermediate The method taught by R.A. Farr et al, J. Org. Chem. 1981 , 46, 1212- 1215, was used in the following two-step preparation. A vigorously stirred solution of 16.5 grams (0.129 mole) of 4-aminocarbonylpiperidine, 25.0 grams (0.135 mole) of 4-propoxyphenylmethyl chloride, and 19.4 grams (0.193 mole) of potassium bicarbonate in 200 mL of toluene was heated at reflux for 6.5 hours. The reaction mixture was then cooled, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with two portions of an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a solid residue, which was slurried in pentane and collected by filtration, yielding 28.2 grams of 4- aminocarbonyl-N-(4-propoxyphenylmethyl)piperidine, mp 142-146 °C. The NMR spectrum was consistent with the proposed structure. A mixture of 27.0 grams (0.10 mole) of 4-aminocarbonyl-N-(4-propoxy- phenylmethyl)piperidine in 200 mL of 1 ,2-dichloroethane was stirred at ambient temperature, and 8.0 grams (0.14 mole) of sodium chloride, followed by 9.2 grams (0.06 mole) of phosphorous oxychloride were added. The reaction mixture was then warmed to reflux, where it stirred for about 1.75 hours. The reaction mixture was cooled to ambient temperature and about 350 mL of water was added. The aqueous layer was separated, washed with two portions of diethyl ether, and then made basic with aqueous 5% sodium hydroxide. The mixture was extracted with two portions of diethyl ether. The combined extracts were washed with an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and poured through a pad of silica gel. The silica gel pad was washed with 1000 mL of diethyl ether. The combined eluants were concentrated under reduced pressure, yielding 14.5 grams of 4-cyano- N-(4-propoxyphenylmethyl)piperidine. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of N-(4-propoxyphenylmethyl)-4-(4-trifluoromethoxy- phenylcarbonyl)piperidine as an intermediate This compound was prepared in a manner analogous to that of Step B of Example 3, with 5.0 grams (0.019 mole) of 4-cyano-N-(4-propoxyphenyl- methyl)piperidine, 10.7 grams (0.045 mole) of 4-trifluoromethoxyphenyl bromide, 1.1 grams (0.045 gram-atom) of magnesium turnings, and iodine (catalyst) in 155 mL of tetrahydrofuran as the reagents. The yield of N-(4- propoxyphenylmethyl)-4-(4-trifluoromethoxyphenylcarbonyl)piperidine was 3.9 grams. The NMR spectrum was consistent with the proposed structure. Step C Synthesis of N-(4-propoxyphenylmethyl)-4-[(4-trifluorometh- oxyphenyl)(4-chlorophenyl)hydroxymethyl]piperidine (Compound 7) A solution of 0.6 gram (0.0014 mole) of N-(4-propoxyphenylmethyl)-4- (4-trifluoromethoxyphenylcarbonyl)piperidine in 15 mL of tetrahydrof uran was stirred, and to the stirred solution was slowly added 1.8 mL of 4-chloro- phenylmagnesium bromide (0.0018 mole-1 M in diethyl ether). Upon completion of addition, the reaction mixture was warmed to 65 °C, where it was stirred for 3.5 hours. After this time the reaction mixture was allowed to cool to ambient temperature, where it stirred for about 18 hours. The reaction mixture was then poured into a mixture of 50 mL of ice and 75 mL of an aqueous solution saturated with ammonium chloride. The mixture was stirred until the ice melted and then extracted with ethyl acetate. The extract was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was dissolved in boiling petroleum ether and treated with decolorizing carbon. Diatoma- ceous earth was stirred in, and the mixture was filtered through a pad of activated magnesium silicate. The magnesium silicate pad was washed with 30% acetone in methylene chloride. The filtrate and wash were com¬ bined and concentrated under reduced pressure, yielding 0.4 gram of N-(4- propoxyphenylmethyl)-4-[(4-trifluoromethoxyphenyl)(4-chlorophenyl)- hydroxymethyljpiperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 5 SYNTHESIS OF N-[4-(2-PROPEN-1-YLOXY)PHENYLMETHYL]-4-[BIS(4- TRIFLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 42) Step A Synthesis of ethyl N-[4-(2-propen-1 -yloxy)phenyl- methyl]piperidin-4-ylcarboxylate as an intermediate The reaction conditions taught by A.E. Moormann, Syn. Comm., 23(6), 789-795 (1993) were used in the following preparation. To a stirred solution of 4.8 grams (0.030 mole) of ethyl piperidin-4-ylcarboxylate and 4.9 grams (0.030 mole) of 4-(2-propen-1-yloxy)benzaldehyde in 50 mL of ethanol was added 3.8 mL (0.030 mole) of borane-pyridine complex. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. The reaction mixture was then taken up in water and extracted with methylene chloride. The organic layer was washed with water and dried with magnesium sulfate. The mixture was filtered and the filtrate concentrated under reduced pressure, yielding 9.0 grams of ethyl N- [4-(2-propen-1-yloxy)phenylmethyl]piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of N-[4-(2-propen-1-yloxy)phenylmethyl]-4-[bis(4-tri- fluoromethoxyphenyl)hydroxymethyl]piperidine (Compound 42) This compound was prepared in a manner analogous to that of Step B of Example 2, with 3.8 grams (0.013 mole) of ethyl N-[4-(2-propen-1 -yloxy)- phenylmethyl]piperidin-4-ylcarboxylate, 15.0 grams (0.063 mole) of 4-triflu- oromethoxyphenyl bromide, 1.5 grams (0.060 gram-atom) of magnesium turnings and about 10 drops of 1 ,2-dibromoethane in diethyl ether as the reagents. The yield of N-[4-(2-propen-1-yloxy)phenylmethyl]-4-[bis(4-triflu- oromethoxyphenyl)hydroxymethyl]piperidine was about 0.3 gram. The NMR spectrum was consistent with the proposed structure. EXAMPLE 6 SYNTHESIS OF N-(2,6-DIMETHOXYPHENYLMETHYL)-4-[BIS(4- TRIFLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 38) Step A Synthesis of 2,6-dimethoxyphenylmethyl bromide as an intermediate After a mixture of 5.7 grams (0.034 mole) of 2,6-dimethoxyphenyl- methanol in 40 mL of concentrated hydrobromic acid was stirred at ambient temperature for about one hour, the reaction mixture was taken up in diethyl ether. Solid sodium chloride was added to the mixture to obtain a phase separation. The organic layer was separated and concentrated under reduced pressure, yielding about 4.7 grams of 2,6-dimethoxyphenylmethyl bromide. This compound was used immediately in the next reaction. Step B Synthesis of ethyl N-(2,6-dimethoxyphenylmethyl)piperidin-4- ylcarboxylate as an intermediate A stirred solution of 4.7 grams (0.020 mole) of 2,6-dimethoxyphenyl- methyl bromide, 3.2 grams (0.020 mole) of ethyl piperidin-4-ylcarboxylate, and 23.5 grams (0.200 mole) of 50% potassium fluoride on Celite® filter aid in 100 mL of acetonitrile was heated at reflux for about 18 hours, after which the reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with mixtures of ethyl acetate in hexane as eluants. The product-containing fractions were combined and concentrated under reduced pressure to a residue. The residue was analyzed using thin layer chromatography, which indicated that the residue was impure. The residue was again subjected to column chromatography on silica gel, with mixtures of ethyl acetate in hexane and methanol in ethyl acetate as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about one gram of ethyl N- (2,6-dimethoxyphenylmethyl)piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure. Step C Synthesis of N-(2,6-dimethoxyphenylmethyl)-4-[bis(4-triflu- oromethoxyphenyl)hydroxymethyl]piperidine (Compound 38) This compound was prepared in a manner analogous to that of Step B of Example 2, with 1.0 gram (0.003 mole) of ethyl N-(2,6-dimethoxyphenyl- methyl)piperidin-4-ylcarboxylate, 3.7 grams (0.015 mole) of 4-trifluorometh- oxyphenyl bromide, 0.4 gram (0.015 gram-atom) of magnesium turnings and 10 drops of 1 ,2-dibromoethane in 20 mL of diethyl ether as reagents, yielding about 0.9 gram of N-(2,6-dimethoxyphenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 7 SYNTHESIS OF N-(4-ETHOXYCARBONYLPHENYLMETHYL)-4-[BIS(4- TRIFLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 57) Step A Synthesis of N-(diethylaminocarbonyl)-4-[bis(4-trifluorometh- oxyphenyl)hydroxymethyl]piperidine as an intermediate This compound was prepared in a manner analogous to that of Example 1 , with 25.7 grams (0.10 mole) of ethyl N-(diethylaminocarbonyl)- piperidin-4-ylcarboxylate, 61.1 grams (0.25 mole) of 4-trifiuoromethoxy- phenyl bromide, and 5.7 grams (0.23 gram-atom) of magnesium turnings in 390 mL of tetrahydrofuran as reagents, yielding 43.8 grams of N-(diethyl- aminocarbonyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine, mp 165-166 °C. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]- piperidine as an intermediate, and N-methyl-4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine (Compound 9) A stirred slurry of 7.7 grams (0.203 mole) of lithium aluminum hydride in 150 mL of dry tetrahydrofuran was cooled to about 15 °C, and a solution of 43.3 grams (0.081 mole) of N-(diethylaminocarbonyl)-4-[bis(4-trifluorometh- oxyphenyl)hydroxymethyl]piperidine in about 250 mL of dry tetrahydrofuran was added dropwise during a 15 minute period. Upon completion of addition, the reaction mixture was stirred at about 15-20 °C for five minutes and then warmed to reflux, where it was stirred for about 18 hours. The reaction mixture was allowed to cool to ambient temperature, where it stood for 24 hours. The reaction mixture was cooled to 0-10 °C, and 7.7 mL of water, 23 mL of aqueous 3N sodium hydroxide, and 7.7 mL of water were in turn added dropwise during a 30 minute period. The reaction mixture temperature was maintained at 0-10 °C throughout these additions. Upon completion of the additions, the reaction mixture was stirred for about 75 minutes and filtered, yielding a sticky solid. The solid was stirred with a small amount of tetrahydrofuran and filtered. The filtrate was concentrated under reduced pressure at 50-55 °C until the viscous residue solidified. The solid was dissolved in warm (31 -33 °C) petroleum ether, and then the solution was cooled in a dry ice/acetone bath. The resultant solid, which precipitated on the walls of the flask, was collected by first decanting away the petroleum ether and then slurrying the solid in diethyl ether. The mixture was concentrated under reduced pressure, yielding 6.8 grams of solid residue. A sample of the solid was subjected to NMR analysis. The NMR spectrum was inconclusive, and the solid was discarded. The petroleum ether decantate was then concentrated under reduced pressure, yielding about 26 grams of sticky residue. The residue was dissolved in warm chloroform and subjected to column chromatography on silica gel. Elution was started with 20% methanol in chloroform. Appropriate fractions, identified by thin layer chromatography, were combined and concentrated under reduced pressure, yielding 9.4 grams of solid, mp 123-128 °C. NMR and mass spectroscopy indicated that this solid was N-methyl-4-[bis(4- trifluoromethoxyphenyl)hydroxymethyl]piperidine (Compound 9). The eluant was changed from 20% methanol in chloroform to 30% methanol in chloro¬ form, and the column chromatography was continued. Other fractions, also identified by thin layer chromatography, were combined and concentrated under reduced pressure, yielding 7.4 grams of solid. NMR and mass spec- trophotometry indicated that this solid was the desired 4-[bis(4- trifluoromethoxyphenyl)hydroxymethyl]piperidine intermediate. Step C Synthesis of N-(4-ethoxycarbonylphenylmethyl)-4-[bis(4-triflu- oromethoxyphenyl)hydroxymethyl]piperidine (Compound 57) By the method of D.A. Walsh et al., J. Med. Chem. 1989, 32, 105-118, a stirred mixture of 0.5 gram (0.001 mole) of 4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]piperidine (prepared in Step B of this Example), 0.3 gram (0.001 mole) of ethyl 4-bromomethylbenzoate, and 0.5 gram (0.004 mole) of potassium carbonate in 15 mL of N,N-dimethylformamide was heated to 95 °C, where it stirred for about 16 hours. After this time the reaction mixture was poured into 50 mL of ice-water, where it stirred for 15 minutes. The mixture was extracted with three 75 mL portions of diethyl ether. The combined extracts were washed with two 75 mL portions of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 0.1 gram of residual oil. The aqueous layer was reextracted with three 100 mL portions of ethyl acetate. The combined extracts were washed with one 100 mL portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 0.8 gram of residual oil, which was subjected to column chromatography on silica gel, with 30% ethyl acetate in heptane as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.3 gram of N-(4-ethoxycarbonylphenyl- methyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 8 SYNTHESIS OF N-(3-CHLORO-4-METHOXYPHENYLMETHYL)-4-[BIS(4- TRIFLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 44) Step A Synthesis of N-(3-chloro-4-methoxyphenylcarbonyl)-4-[bis(4- trifluoromethoxyphenyl)hydroxymethyl]piperidine as an intermediate A stirred solution of 0.22 gram (0.0012 mole) of 3-chloro-4-methoxy- benzoic acid in a small amount of tetrahydrofuran and chloroform was cooled to 0 °C, and 0.12 mL (0.0014 mole) of oxalyl chloride was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature, where it was stirred for about 3.5 hours. After this time the reaction mixture was concentrated under reduced pressure, yielding 3-chloro-4-methoxybenzoyl chloride, which was dissolved in a small amount of tetrahydrofuran for later use. In a separate reaction vessel, a solution of 0.5 gram (0.0012 mole) of 4- [bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine (prepared in Step B of Example 7) and 0.09 gram (0.0012 mole) of pyridine in a small amount of tetrahydrofuran was stirred, and the solution of 3-chloro-4-methoxybenzoyl chloride in tetrahydrofuran, prepared above, was added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 15 minutes and then filtered to remove a white solid. The filtrate was stirred for about 18 hours and then was partitioned between ethyl acetate and an aqueous solution saturated with sodium chloride. The organic layer was separated and passed through a column of silica gel. Elution was accomplished with 50% ethyl acetate in hexane. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.62 gram of N-(3-chloro-4-methoxyphenylcarbonyl)-4-[bis(4- trifluoromethoxyphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of N-(3-chloro-4-methoxyphenylmethyl)-4-[bis(4-tri- fluoromethoxyphenyl)hydroxymethyl]piperidine (Compound 44) To a stirred solution of 0.50 gram (0.0008 mole) of N-(3-chloro-4- methoxyphenylcarbonyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]- piperidine in 5 mL of tetrahydrofuran was slowly added 0.42 mL (0.0040 mole) of borane-methyl sulfide complex (10M in BH3). Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. The reaction mixture was then cooled in an ice-bath, and 20 mL of methanol was added slowly to quench the reaction. The reaction mixture was then concentrated under reduced pressure to a residue. Another 20 mL of methanol was stirred with the residue, and this was concentrated under reduced pressure to the residue. The process of adding 20 mL of methanol and concentrating the solution to the residue was repeated once more. The residue was partitioned between ethyl acetate and water, and the mixture was stirred for 15 minutes. The organic layer was separated, washed with an aqueous solution saturated with sodium chloride, and then dried with sodium sulfate. The mixture was filtered and concentrated under reduced pressure to a residue, which was subjected to column chromatog¬ raphy on silica gel, with mixtures of ethyl acetate in hexane as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.13 gram of N-(3-chloro-4-methoxyphenyl- methyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 9 SYNTHESIS OF N-[4-(2-PROPEN-1-YLOXY)PHENYLMETHYL]-4-[BIS(4- TRIFLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE N-OXIDE (COMPOUND 43) To a stirred solution of 0.5 gram (0.0008 mole) of N-[4-(2-propen-1- yloxy)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperi- dine (Compound 42, prepared in Example 5) in 10 mL of chloroform was added 0.3 gram (0.0008 mole) of 50% 3-chloroperoxybenzoic acid. Upon completion of addition, the reaction mixture was stirred at ambient temper¬ ature for about 2 hours. After this time the reaction mixture was washed, first, with an aqueous solution saturated with sodium bicarbonate, and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with mixtures of ethyl acetate and hexane as eluants. The product-containing fractions were combined and concentrated under reduced pressure to a residue. The residue was concentrated further under high vacuum, yielding about 0.2 gram of N-[4-(2- propen-1-yloxy)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxy- methyljpiperidine N-oxide. The NMR spectrum was consistent with the proposed structure. EXAMPLE 10 SYNTHESIS OF N-(4-PROPOXYPHENYLMETHYL)-4-[BIS(4-TRI- FLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 29) Step A Synthesis of ethyl N-(4-propoxyphenylmethyl)piperidin-4- ylcarboxylate as an intermediate This compound was prepared in a manner analogous to that of Step A of Example 2, with 5.3 grams (0.032 mole) of 4-propoxybenzaldehyde, 5.0 grams (0.032 mole) of ethyl piperidin-4-ylcarboxylate, 2.0 grams (0.032 mole) of sodium cyanoborohydride, and methanolic hydrogen chloride solution in 30 mL of methanol as the reagents. The yield of ethyl N-(4-pro- poxyphenylmethyl)piperidin-4-ylcarboxylate was 2.6 grams. The NMR - 28 - spectrum was consistent with the proposed structure. Step B Synthesis of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine (Compound 29) 5 This compound was prepared in a manner analogous to that of Example 1 , with 1.5 grams (0.005 mole) of ethyl N-(4-propoxyphenyl- methyl)piperidin-4-ylcarboxylate, 3.6 grams (0.015 mole) of 4-trifluorometh- oxyphenyl bromide, 0.4 gram (0.015 gram-atom) of magnesium turnings, and iodine (catalyst) in 40 mL of tetrahydrofuran as the reagents. The yield 10 of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxy- methyl]piperidine was 1.1 grams. The NMR spectrum was consistent with the proposed structure. EXAMPLE 11 15 SYNTHESIS OF N-[4-(2-PROPYN-1 -YLOXY)PHENYLMETHYL]-4-[BIS(4- TRI-FLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 65) Step A Synthesis of 4-[bis(4-trifluoromethoxyphenyl)hydroxy- methyljpyridine as an intermediate 20 This compound was prepared in a manner analogous to that of Example 1 , with 10.9 grams (0.067 mole) of ethyl pyridin-4-ylcarboxylate, 40.3 grams (0.167 mole) of 4-trifluoromethoxyphenyl bromide, and 4.1 grams (0.023 gram-atom) of magnesium turnings in about 275 mL of diethyl ether as reagents. The crude product was subjected to column chromatog- 25 raphy on silica gel, with mixtures of 20-90% ethyl acetate in hexane. The product-containing fractions were combined and concentrated under reduced pressure to a residual solid. The solid was triturated three times with hexane, yielding 17.7 grams of 4-[bis(4-trifluoromethoxyphenyl)- hydroxymethyljpyridine. The NMR spectrum was consistent with the 30 proposed structure. Step B Synthesis of 4-[bis(4-trifluoromethoxyphenyl)hydroxy- methyljpyridine hydrochloride as an intermediate To a stirred solution of 17.6 grams (0.041 mole) of 4-[bis(4-triflu- 35 oromethoxyphenyl)hydroxymethyl]pyridine in 200 mL of diethyl ether was added about 20 mL of an ethanolic solution saturated with hydrogen chloride. Upon completion of addition, the reaction mixture was cooled to promote precipitation of the product. When the solid precipitate did not appear, the reaction mixture was slowly concentrated during a one hour period by passing a stream of nitrogen gas over the reaction mixture. During this time the solid precipitate still did not appear. Additional diethyl ether was added, and the stream of nitrogen gas over the reaction mixture was continued. The reaction mixture was finally concentrated under reduced pressure to near dryness, at which point a solid precipitate formed. The solid was slurried in about 10 mL of fresh diethyl ether and filtered to yield 9.3 grams of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]pyridine hydrochloride. The NMR spectrum was consistent with the proposed structure. Step C Synthesis of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]- piperidine hydrochloride as an intermediate A solution of 2.0 grams (0.004 mole) of 4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]pyridine hydrochloride and a catalytic amount of platinum oxide in 125 mL of methanol was hydrogenated at 50 psi of hydrogen in a Parr hydrogenator. The completion of hydrogenation required about two hours. After this time, the reaction mixture was filtered to remove the catalyst. The filtrate was concentrated to about 20 mL in volume, 80 mL of diethyl ether was added, and the solution was placed in a refrigerator. The resultant solid precipitate was collected by filtration, yielding about 0.4 gram of product. The filtrate was concentrated under reduced pressure, yielding an additional 1.9 grams of product. The two solid fractions were combined, yielding 2.3 grams of 4-[bis(4-trifluorometh- oxyphenyl)hydroxymethyl]piperidine hydrochloride. The NMR spectrum was consistent with the proposed structure. Step D Synthesis of N-[4-(2-propyn-1-yloxy)phenylmethyl]-4-[bis(4-tri- fluoromethoxyphenyl)hydroxymethyl]piperidine (Compound 65) A stirred mixture of 0.8 gram (0.0016 mole) of 4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]piperidine hydrochloride, 0.3 gram (0.0016 mole) of 4-(2-propyn-1-yloxy)phenylmethyl chloride and 0.5 gram (0.0079 mole) of potassium fluoride on Celite® filter aid in 50 mL of acetonitrile was heated at reflux for about 1.3 hours. After this time 0.5 mL (excess) of triethyl- amine was added, and the reaction mixture became homogeneous. Upon completion of addition, the reaction mixture was heated at reflux for an additional 18 hours. After this time the reaction mixture was cooled, filtered, and the filtrate concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with mixtures of 10- 70% diethyl ether in hexane as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.6 gram of N-[4-(2-propyn-1 -yloxy)phenylmethyl]-4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 12 SYNTHESIS OF N-[4-(METHYLCARBONYLAMINO)PHENYLMETHYL]-4- [BIS(4-TRIFLUOROMETHOXYPHENYL)HYDROXYMETHYL]PIPERIDINE (COMPOUND 66) Step A Synthesis N-phenylmethyl-4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]piperidine (Compound 13) as an intermediate This compound was prepared in a manner analogous to that of Step B of Example 3, with 6.0 grams (0.024 mole) of ethyl N-phenylmethylpiperidin- 4-ylcarboxylate, 1.8 grams (0.073 gram-atom) of magnesium turnings, and 17.5 grams (0.073 mole) of 4-trifiuoromethoxyphenyl bromide in about 80 mL of tetrahydrofuran as reagents. The yield of N-phenylmethyl-4-[bis(4- trifluoromethoxyphenyl)hydroxymethyl]piperidine was 9.7 grams. The NMR spectrum was consistent with the proposed structure. Step B Synthesis N-phenylmethyl-4-[bis(4-trifluoromethoxyphenyl)- hydroxymethyljpiperidine hydrochloride as an intermediate The reaction conditions taught by P.J. Gilligan et al., J. Med. Chem. 1992, 4344-4361 , were used in the following two-step preparation. A stirred solution of 1.0 gram (0.002 mole) of N-phenylmethyl-4-[bis(4-trifluorometh- oxyphenyl)hydroxymethyl]piperidine in 30 mL of diethyl ether was cooled to 0 °C, and hydrogen chloride gas was bubbled in. An oily solid precipitate formed. Upon completion of precipitation, the reaction mixture was taken up in 25 mL of hexane and stored in a refrigerator for about 18 hours. After this time the supernatant liquid was decanted from the precipitate. The precipitate was then stirred with about 20 mL of diethyl ether, and the mixture was concentrated under reduced pressure to a residue. The solid residue was stirred with about 20 mL of hexane, which was then decanted from the solid. The solid was dried under reduced pressure, yielding 0.8 gram of N-phenylmethyl-4-[bis(4-trifluoromethoxyphenyl)- hydroxymethyljpipendine hydrochloride. The NMR spectrum was consistent with the proposed structure. Step C Synthesis 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]- piperidine as an intermediate Under a nitrogen atmosphere, 0.8 gram of 10% palladium on charcoal (catalyst) was placed in the reaction vessel. To this were cautiously added 25 mL of nitrogen-purged methanol, a solution of 0.8 gram (0.001 mole) of N-phenylmethyl-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine hydrochloride in 10 mL of methanol, and then 0.9 gram (0.010 mole) of ammonium formate. Upon completion of addition, the reaction mixture was heated at reflux for about 45 minutes. The reaction mixture was then cooled to ambient temperature and diluted with 1 :1 -methylene chloride/- methanol. The mixture was filtered through a pad of diatomaceous earth/fiberglass, and the filtrate was concentrated at about 30 °C under reduced pressure to a residue. The residue was taken up in about 70 mL of ice/water and made basic with aqueous 5% sodium hydroxide solution. The mixture was extracted with methylene chloride, and the extract was washed with an aqueous solution saturated with sodium chloride. The organic layer was then dried with sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was stirred with petroleum ether, and 0.5 gram of solid 4-[bis(4-trifluoromethoxy- phenyl)hydroxymethyl]piperidine was collected by filtration. The NMR spectrum was consistent with the proposed structure. Step D Synthesis of N-[4-(methylcarbonylamino)phenylmethyl]-4-[bis- (4-trifluoromethoxyphenyl)hydroxymethyl]piperidine (Compound 66) To a stirred solution of 0.4 gram (0.0008 mole) of 4-[bis(4-trifluoro- methoxyphenyl)hydroxymethyl]piperidine in 10 mL of dimethyl sulfoxide was added a mixture of 0.2 gram (0.0008 mole) of 4-(methylcarbonylamino)- phenylmethyl chloride and 0.6 mL (0.003 mole) of N,N-diisopropylethyl- amine. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. After this time the reaction mixture was partitioned between an aqueous solution saturated with sodium bicarbonate and ethyl acetate. The organic layer was separated and washed with an aqueous solution saturated with sodium chloride. The organic layer was then concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with methylene chloride and mixtures of 10-50% acetone in methylene chloride as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about 0.3 gram of N-[4- (methylcarbonylamino)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)- hydroxymethyljpiperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 13 SYNTHESIS OF N-(4-PROPOXYPHENYLMETHYL)-4-[BIS(4-TRI- FLUOROMETHOXYPHENYL)METHYL]PIPERIDINE (COMPOUND 104) Step A Synthesis of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)mercaptomethyl]piperidine as an intermediate Under a nitrogen atmosphere, a solution of 2.3 grams (0.004 mole) of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]- piperidine (prepared in Example 10) in about 13.4 mL of 1 ,2-dimethoxy- ethane was stirred, and 1.3 grams (0.003 mole) of 2,4-bis(4-methoxy- phenyl)-1 ,3-dithia-2,4-diphosphetane-2,4-disulfide (Lawesson's Reagent) was added. The reaction mixture was then warmed to about 80-85 °C, and an additional 0.3 gram (0.0007 mole) of Lawesson's Reagent was added. The reaction mixture was stirred for 10 minutes, and another 0.3 gram 33 - (0.0007 mole) of Lawesson's Reagent was added. After the reaction mixture was stirred for another 10 minutes, a third 0.3 gram (0.0007 mole) amount of Lawesson's Reagent was added. The 1 ,2-dimethoxyethane solvent was removed by azeotroping it with methylene chloride. The resultant methylene chloride solution was concentrated under reduced pressure to a residue, which was added to the crude product of a previous run (0.001 mole) of this reaction. The combined products were subjected to column chromatography on silica gel, with a 2:1 :1 mixture of toluene, methylene chloride, and acetone, respectively, as eluants. The product- containing fractions were combined and concentrated under reduced pressure, yielding about 3.8 grams of impure product. The product was again subjected to column chromatography on silica gel, with methylene chloride and 1-2% mixtures of acetone in methylene chloride as the eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 1.2 grams of N-(4-propoxyphenylmethyl)-4- [bis(4-trifluoromethoxyphenyl)mercaptomethyl]piperidine. The NMR spectrum was consistent with the proposed structure. Step B Synthesis of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)methyl]piperidine as an intermediate (Compound 104) To a stirred mixture of 15.4 grams (excess) Raney® nickel (50% slurry in water), 7.7 mL of 1 ,3-cyclohexadiene, and 13.1 mL of concentrated ammonium hydroxide in 105 mL of methanol was added a solution of 0.8 gram (0.0013 mole) of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluorometh- oxyphenyl)mercaptomethyl]piperidine in 50 mL of ethanol. Upon completion of addition, the reaction mixture was warmed to reflux, where it was stirred for about 30 minutes. The reaction mixture was then cooled and combined with two small (0.00017 mole each) earlier runs of this reaction. The combination was filtered through a pad of diatomaceous earth. The pad of diatomaceous earth was then washed with ethanol, and the wash and filtrate were combined. The wash/filtrate combination was concentrated under reduced pressure to a residue, which was diluted with ethyl acetate and washed with an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with methylene chloride and 2-4% acetone in methylene chloride as the eluants. The product- containing fractions were combined and concentrated under reduced pressure, yielding 0.3 gram of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)methyl]piperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 14 SYNTHESIS OF N-(4-METHOXYPHENYLMETHYL)-4-[BIS(4- ETHYLPHENYL)METHYL]PIPERIDINE (COMPOUND 103) To a stirred solution of 1.0 gram (0.002 mole) of N-(4-methoxyphenyl- methyl)-4-[bis(4-ethylphenyl)hydroxymethyl]piperidine (prepared in the manner of Example 1 ) in 10 mL of methylene chloride was slowly added 1.1 mL (0.007 mole) of triethylsilane, followed by 1.0 mL (0.013 mole) of trifluoroacetic acid. The reaction mixture was then stirred at ambient temperature during a five hour period. After this time the reaction mixture was neutralized with solid sodium carbonate. The mixture was then partitioned between 100 mL of methylene chloride and 50 mL of water. The organic layer was separated and washed with two 50 mL portions of an aqueous solution saturated with sodium chloride. The organic layer was then dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was purified by subjecting it to preparative thin layer chromatography, with 25% acetone in methylene chloride as the eluant, yielding about 0.5 gram of N-(4-methoxyphenyl- methyl)-4-[bis(4-ethylphenyl)methyl]piperidine. The NMR spectrum was consistent with the proposed structure. EXAMPLE 15 SYNTHESIS OF N-(4-PROPOXYPHENYLMETHYL)-4-[BIS(4-TRI- FLUOROMETHOXYPHENYL)FLUOROMETHYL]PIPERIDINE (COMPOUND 105) A stirred solution of 0.6 gram (0.001 mole) of N-(4-propoxyphenyl- methyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine (prepared in Example 10) in 15 mL of methylene chloride was cooled to -78 °C, and 0.15 mL (0.001 mole) of diethylaminosulphur trifluoride (DAST) was added via a syringe. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature as it stirred for about 18 hours. After this time, the reaction mixture was poured into ice-water. The mixture was then extracted with two 50 mL portions of methylene chloride. The combined extracts were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was sub- jected to column chromatography on silica gel, with mixtures of 5-15% acetone in methylene chloride as the eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about 0.1 gram of N-(4-propoxyphenylmethyl)-4-[bis(4-trifluoro- methoxyphenyl)fluoromethyl]piperidine. The NMR spectrum was consistent with the proposed structure. Representative compounds prepared by the methods exemplified above are listed in Table 1. Characterizing properties are given in Table 2. Biological Data Candidate insecticides were incorporated into an artificial diet for evaluation of insecticidal activity against the tobacco budworm (Heliothis virescens [Fabricius]) in the following manner. Stock solutions of test chemical in dimethyl sulfoxide, ranging from 50 micromolar to 0.005 micromolar, were prepared for each rate of application. One hundred microliters of each of the stock solutions was manually stirred into 50 mL of a molten (65-70°C) wheat germ-based artificial diet. The 50 mL of molten diet containing the test chemical was poured evenly into twenty wells in the outer two rows on each side of a twenty-five well, five row plastic tray. (Each well in the tray was about 1 cm in depth, with an opening of 3 cm by 4 cm at the lip.) Molten diet containing only dimethyl sulfoxide at the levels used in the test chemical-treated diet was poured into the five wells in the third (center) row of the tray. Each tray therefore contained one test chemical at a single rate of application, together with an untreated control. The rates of application, expressed as the negative log of the molar concentration, and the corresponding concentrations of the stock solution prepared for each rate are shown below: Stock Solution Rate of Application 50 micromolar 4 5 5 0.5 6 0.05 7 0.005 8 Single second instar tobacco budworm larvae, selected at a stage of growth at which they uniformly weigh about 5 mg each, were placed in each well. Upon completion of infestation, a sheet of clear plastic was heat- sealed over the top of the tray by use of a common household flat iron. The trays were held at 25°C at 60% relative humidity for five days in a growth chamber. Lighting was set at 14 hours of light and 10 hours of darkness. After the 5-day exposure period, mortality counts were taken, and the surviving insects were weighed. From the weights of the surviving insects that fed on the treated diet as compared to those insects that fed on the untreated diet, the percent growth inhibition caused by each test chemical was determined. From these data, the negative log of the concentration of the test chemical that provided 50% growth inhibition (plso) was determined by linear regression, when possible, for each test chemical. Also, where possible, the negative log of the concentration of the test chemical that provided 50% mortality (pLCso) was determined. Candidate insecticides with high plso values from the diet test were tested for insecticidal activity in foliar evaluations against tobacco budworm, beet armyworm (Spodoptera exigua [Hubner]), and cabbage looper (Trichoplusia ni [Hubner]). In these tests against tobacco budworm and beet armyworm, nine-day- old chick pea plants (Cicer arietinum) were sprayed at 20 psi to runoff on both upper and lower leaf surfaces with solutions of test chemical to provide application rates as high as 1000 ppm of test chemical. The solvent used to prepare the solutions of test chemical was 10% acetone or methanol (v/v) and 0.1% of the surfactant octylphenoxypolyethoxyethanol in distilled water. Four replicates, each containing one chick pea plant, for each rate of application of test chemical were sprayed. The treated plants were transferred to a hood, where they were kept until the spray had dried. The four chick pea plants for each replicate treated with test chemical as described above were removed from their pots by cutting the stems just above the soil line. The excised leaves and stems from the four plants in each replicate were placed in individual 8-ounce paper cups, each containing a moistened filter paper. Five second-instar (6 days old) tobacco budworms or beet armyworms (7-8 days old) were counted into each cup, taking care not to cause injury. An opaque plastic lid was placed on each cup, which was then held in a growth chamber for a 96 hour exposure period at 25°C and 50% relative humidity. At the end of the 96 hour exposure period the cups were opened, and the numbers of dead, moribund, and live insects were counted. Using the insect counts, the efficacy of the test chemical was expressed in percent control. Percent control is derived from the total number of dead insects (TD) plus the total number of moribund insects (TM) as compared to the total number of insects (Tl) in the test: «/ - . TD+TM J ΛΛ % Control = — -γj — x 100 The condition of the test plants was also observed for phytotoxicity and for reduction of feeding damage as compared to an untreated control. Foliar tests with cabbage looper were conducted in the same manner as described above, the difference being that pinto bean plants (Phaseolus vulgaris) were used in place of chick pea plants. The compounds of the present invention were active in the diet test against the tobacco budworm. Compounds 22, 24, 27, 28, 29, 34, 39, 42, 43, 46, 47, 48, 52, 55, 57, 65, 68, 78, 79, 80, 88, 89, 90, 92, 94, 96, 97, 98, and 102 all exhibited plso values of 6.0 or greater. Table 3 gives the insecticidal activity data for compounds tested in the diet test. The compounds of the present invention also showed good to excellent insecticidal activity in the foliar test against tobacco budworm, beet armyworm, and cabbage looper. It can be seen from Table 4 that many compounds provided 80% control or greater of one or more of the test insect species at an application rate of 100 ppm in the foliar test. For insecticidal application, the active compounds are formulated into insecticidal compositions by admixture in insecticidally effective amount with adjuvants and carriers normally employed in the art for facilitating the dispersion of active ingredients for the particular utility desired, recognizing the fact that the formulation and mode of application of a toxicant may affect the activity of the material in a given application. Thus, for agricultural use the present insecticidal compounds may be formulated as granules of relatively large particle size, as water-soluble or water-dispersible granules, as powdery dusts, as wettabie powders, as emulsifiable concentrates, as solutions, or as any of several other known types of formulations, depending on the desired mode of application. These insecticidal compositions may be applied either as water-diluted sprays, or dusts, or granules to the areas in which insect control is desired. These formulations may contain as little as 0.1%, 0.2% or 0.5% to as much as 95% or more by weight of active ingredient. Dusts are free flowing admixtures of the active ingredients with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shell and cottonseed flours, and other organic and inorganic solids which act as dispersants and carriers for the toxicant; these finely divided solids have an average particle size of less than about 50 microns. A typical dust formulation useful herein is one containing 1.0 part or less of the insecticidal compound and 99.0 parts of talc. Wettabie powders are in the form of finely divided particles which disperse readily in water or other dispersant. The wettabie powder is ultimately applied to the locus where insect control is desired either as a dry dust or as an emulsion in water or other liquid. Typical carriers for wettabie powders include Fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet, inorganic diluents. Wettabie powders normally are prepared to contain about 5-80% of active ingredient, depending on the absorbency of the carrier, and usually also contain a small amount of a wetting, dispersing, or emulsifying agent to facilitate dispersion. For example, a useful wettabie powder formulation contains 80.8 parts of the insecticidal compound, 17.9 parts of Palmetto clay, and 1.0 part of sodium 40 soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene, or other organic solvents. Granular formulations, wherein the toxicant is carried on relatively coarse particles, are of particular utility for aerial distribution or for penetration of cover crop canopy. Pressurized sprays, typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low boiling dispersant solvent carrier, such as carbon dioxide, propane, or butane, may also be used. Water-soluble or water-dispersible granules are also useful formulations for insecticidal application of the present compounds. Such granular formulations are free-flowing, non-dusty, and readily water-soluble or water-miscible. The soluble or dispersible granular formulations described in U.S. patent No. 3,920,442 are useful herein with the present insecticidal compounds. In use by the farmer on the field, the granular formulations, emulsifiable concentrates, flowable concentrates, solutions, etc., may be diluted with water to give a concentration of active ingredient in the range of say 0.1 % or 0.2% to 1.5% or 2%. The active insecticidal compounds of this invention may be formulated and/or applied with other insecticides, fungicides, nematicides, plant growth regulators, fertilizers, or other agricultural chemicals. In using an active compound of this invention, whether formulated alone or with other agricultural chemicals, to control insects, an effective amount and concentration of the active compound is applied to the locus where control is desired. The locus may be, e.g., the insects themselves, plants upon which the insects feed, or the insect habitat. When the locus is the soil, e.g., soil in which agricultural crops have been or will be planted, the composition of the active compound may be applied to and optionally incorporated into the soil. For most applications the effective amount may be as low as, e.g. about 10 to 500 g/ha, preferably about 100 to 250 g/ha. It is apparent that various modifications may be made in the formulation and application of the compounds of this invention without departing from the inventive concepts herein as defined inventive concepts herein as defined in the claims. - 39 lignosulfonate and 0.3 part of sulfonated aliphatic polyester as wetting agents. Other useful formulations for insecticidal applications are emulsifiable concentrates (ECs) which are homogeneous liquid compositions dispersible in water or other dispersant, and may consist entirely of the insecticidal compound and a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone, or other non-volatile organic solvent. For insecticidal application these concentrates are dispersed in water or other liquid carrier, and normally applied as a spray to the area to be treated. The percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95% of active ingredient by weight of the insecticidal composition. Flowable formulations are similar to ECs except that the active ingredient is suspended in a liquid carrier, generally water. Flowables, like ECs, may include a small amount of a surfactant, and contain active ingredient in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition. For application, flowables may be diluted in water or other liquid vehicle, and are normally applied as a spray to the area to be treated. Typical wetting, dispersing, or emulsifying agents used in agricultural formulations include, but are not limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylaryl polyether alcohols; sulfated higher alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of long-chain mercaptans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. The surface-active agents, when used, normally comprise from 1 to 15% by weight of the composition. Other useful formulations include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol, or other suitable solvents. Still other useful formulations for insecticidal applications include simple solutions of the active ingredient in a solvent in which it is completely Table 1 Insecticidal N-(substituted al yl)-4-[di(substituted)hydroxymethyl]piperidines Where n is 1 , and R is and V, W, Y, and Z are hydrogen Cmpd. No. X R1 R2 n-OC3-H7 cyclopropyl 3 Cmpd. No. R R2 n-OC3H7 phenyl 3 . Where n is 1 , and R 1 and R^ are Cmpd. No. R 9 H 10 cyclopropyl 11 cyciohexyl 12 pyridin-4-yl Cmpd.No. n V W X 13 H H H H H 14 Cl H H H H 15 H H Cl H H 16 H 17 H 18 H 19 H 20 H 21 H 22 H 23 H 24 H Cmpd.No. n V W X 25 H H -OCH3 H H 26 H H -OCH3 H H 27 H -OC-2H5 H H H 28 H H -OC-2H5 H H 29 H H n-OC-3H7 H H 30 31 32 33 34 35 36 37 38 39 40 41 Cmpd.No. n V W Where n is 1 , and R is and V, W, Y, and Z are hydrogen Cmpd. No. R1 R2 ; Where n is 1 , and R 1 and R 2 are Cmpd. No. 73 -CH -C(CI)=C(CI)2 Cmpd. No. R Cmpd.No. n V W X Y 78 H H n-OC4Hg H H 79 H H -OCH2CH(CH3)2 H H 80 H H H H -OCH > -- 81 H H n-OCδHn H H 82 Cl H n-OC3H7 H H Cmpd.No. n V W 83 -C 2 H 5 H n-OC3H7 H H 84 -CF3 H n-OC3H7 H H 85 H -CH3 n-OC3H7 H H 86 H -C2H5 n-OC3H7 H H 87 H H -0(CH2)3N(CH3) H H 88 H H -OCH 2 C(CI)=CH2 H H 89 H H -OCH2CH=CHCI H H cis Isomer 90 H H -OCH2CH=CHCI H H trans Isomer 91 H H -OCH2CH=CCI H H 92 H H -OCH2C(CH3)=CH2 H H 93 H H -OCH2CH=C(CH3) 2 H H 94 H H -OCH2CH=C(CH 3 ) 2 H H an N-oxide Cmpd.No. n V W 95 H H -0(CH2)3CH=CH2 H H 96 H H -OCH2C≡N H H 97 H H -OCH2OCH H H an N-oxide 98 H H -OCH2C≡CCH3 H H 99 H H -SO2C2F5 H H 100 H H -NH2 H H 101 H H -NHC3H7 H H 102 1 H H -NH(C=0)C2H5 H H Where n is 1 , and R is and V, W, Y, and Z are hydrogen Cmpd. No.. R1 R2 Where n is 1 , and R is and V, W, Y, and Z are hydrogen Cmpd. No. R R2 Table 3 Insecticidal Activity When Incorporated into the Diet of Tobacco Budworm Cm d. No. 6 Table 3 (continued) Table 3 (continued) 60 Footnotes The rate of application is expressed as the negative log of the molar concentration of the test compound in the diet. Percent growth inhibition is derived from the total weight of the insects (IW) at each rate of application in the test relative to the total weight of insects in an untreated control, % Gr. Inh. = [IW (control) - IW (test) / IW (control)] x 100 A minus % growth inhibition indicates that the insects weighed more at the termination of the test than those in the untreated control. pl50 is the negative log of the concentration of the test chemical that provides 50% growth inhibition in the test insects. Percent mortality is derived from the number of dead insects (TD) relative to the total number of insects (Tl) used in the test, TD % Mortality = ^ j- x 100 PLC50 is the negative log of the concentration of the test chemical that provides 50% mortality of the test insects. a Average of 3 tests. b Average of 2 tests. -61 - Table 4 Table 4 (continued) Percent control is derived from the total number of dead insects (TD) plus the total number of moribund insects (TM) as compared to the total number of insects (Tl) in the test: c T -. x , TD+TM J ΛΛ % Control = — yj — x 100 TBW is tobacco budworm {Heliothis virescens [Fabricius]) CL is cabbage looper (Trichoplusia ni [Hubner]. BAW is beet armyworm (Spodoptera exigua [Hubner]. indicates an average of more than one test.

Claims: Claims 1. A compound of the formula: in which Q is selected from hydrogen, hydroxy, and fluorine; R is selected from a heteroaryl having 5 or 6 ring atoms and 1 or 2 hetero atoms, and characterized in that V is selected from hydrogen, halogen, alkyl, haloalkyl, and alkoxy; W is selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, phenoxy, and phenylalkoxy; X is selected from hydrogen, hydroxy, halogen, alkyl, alkoxyalkyl, alkoxy, cycloalkylalkoxy, haloalkoxy, alkenyloxy, haloalkenyloxy, alkynyloxy, alkylsilyloxy, alkylthio, haloalkylthio, cyano, cyanoalkoxy, nitro, amino, monoalkylamino, dialkylamino, alkylaminoalkoxy, alkylcarbonylamino, alkoxycarbonylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, aminocarbonyloxy, phenyl, phenylalkoxy, phenoxy, and phenoxyalkyi, each phenyl ring optionally substituted with halogen, alkoxy, or haloalkoxy; Y and Z are independently selected from hydrogen and alkoxy; W and X taken together may be -OCH2CH2O-, -CH2C(CH3)2θ-, or -OC(CH3)2θ-; R and R 2 are independently selected from phenyl substituted with halogen, alkyl, haloalkyl, haloalkoxy, alkylsulfonyloxy, and haloalkylsulfon¬ yloxy; and n is 1 , 2, or 3; with the proviso that each aliphatic moiety contains not more than 6 carbon atoms, halogen means chlorine or fluorine, and each alkyl substituent on an amino nitrogen contains 1 to 3 carbon atoms, and the corresponding N-oxides and agriculturally acceptable salts. 2. A compound of claim 1 in which R is characterized in that V is selected from hydrogen and halogen; V and Z are each hydrogen; W is selected from hydrogen, halogen, and alkoxy; and X is selected from hydrogen, hydroxy, halogen, alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, alkenyloxy alkynyloxy, haloalkoxy, alkylthio, haloalkylthio, monoalkylamino, dialkylamino, alkoxyalkyl, alkoxyalkoxy, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, alkylcarbonylamino, cyano, phenyl, phenoxy, phenoxyalkyi, and optionally substituted phenylalkoxy; W and X taken together may be -OCH2CH2O-, -CH2C(CH3)2θ-, or -OC(CH 3 )2θ-; R and R 2 are independently selected from phenyl substituted with halogen or haloalkoxy; and n is 1 , 2, or 3, with the proviso that one of R 1 and R 2 is phenyl substituted in the para position, and the corresponding N-oxides and agriculturally acceptable salts. 3. A compound of claim 2 characterized in that V is selected from hydrogen and fluorine; W is selected from hydrogen, halogen, methoxy and ethoxy ; X is selected from hydrogen, halogen, methyl, methoxy, ethoxy, n-pro- poxy, n-butoxy, perfluoroethoxy, perfluoroethylthio, cyano, phenyl, phenoxy, phenylmethoxy, dimethylamino, ethoxymethyl, ethylcarbonyl, ethoxycarbon- yl, allyloxy, propargyloxy, 2-methylpropoxy, cyclopropylmethoxy, 2-chloro-2- propenoxy, 2-methyl-2-propenoxy, 3-methyl-2-butenoxy, cyanomethoxy, 2- butynoxy, and ethylcarbonylamino; W and X taken together may be -CH2C(CH3)2θ-; n is 1 ; and R 1 and R 2 are each p-trifluoromethoxyphenyl; and the corresponding N-oxides and agriculturally acceptable salts. 4. A compound of claim 3 characterized in that W is selected from hydrogen, fluorine, and methoxy. 5. A compound of claim 4 characterized in that W is hydrogen. 6. A compound of claim 5 characterized in that V is hydrogen, and X is n-propoxy, cyclopropylmethoxy, ethoxycarbonyl, or ethoxy, and the corresponding N-oxides. 7. The compound of claim 6 that is N-(4-ethoxyphenyimethyl)-4- [bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. 8. The compound of claim 6 that is N-(4-n-propoxyphenylmethyl)-4- [bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. 9. The compound of claim 6 that is N-(4-ethoxycarbonylphenyl- methyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. 10. The compound of claim 6 that is N-(4-cyclopropylmethoxy- phenylmethyl)-4-[bis(4-thfluoromethoxyphenyl)hydroxymethyl]piperidine. 11. The compound of claim 6 that is N-(4-n-propoxyphenylmethyl)-4- [bis(4-thfluoromethoxyphenyl)hydroxymethyl]piperidine N-oxide 12. The compound of claim 6 that is N-(4-cyclopropylmethoxy- phenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine N- oxide. 13. A composition containing an insecticidally effective amount of a compound of claim 1 in admixture with at least one agriculturally acceptable extender or adjuvant. 14. A method of controlling insects characterized bycomprises applying to the locus where control is desired an insecticidally effective amount of a composition of claim 13.

Inventors: ALI SYED F, COHEN DANIEL H, LYGA JOHN W, SILVERMAN IAN R, SZCZEPANSKI STEVEN W, ALI, SYED, F., COHEN, DANIEL, H., LYGA, JOHN, W., SILVERMAN, IAN, R., SZCZEPANSKI, STEVEN, W.
Applicants: FMC CORP, FMC CORPORATION
Application year: 1995
Main classification: A01N43
IPC codes: A01N43, A01N47, A01N55, C07D211, C07D401, C07D405, C07D409, C07D413, C07F7