The pyrethrins and related compounds. XIX Geometrical and optical isomers of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid and insecticidal esters with 5-benzyi-3-furylmethyi and 3-phenoxybenzyl alcohols

Esters of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxylic acid with appropriate alcohols are more active insecticides than the corresponding 3-isobutenyl compounds (chrysanthemates). (±)-Cis and (±)-trans forms of the dichloro acid are obtained by fractional crystallisation of the mixed acids or by hydrolysis of the ethyl esters separated by fractional distillation. The (±)-cis and (±)-trans acids are resolved into their (+)- and (-)-forms with α-methyl-benzylamine and threo-l-p-nitrophenyl-2-N,N-dimethyiamino-propane-1,3-diol respectively. As for the corresponding chrysanthemates, the (+)-cis and (+)-trans acids give esters more active as insecticides than their enantiomers.     

The pyrethrins and related compounds. Part XXX: Esters from acids with mono-halovinyl side chains

Esters of 3-phenoxybenzyl alcohol and its α-cyano derivative with 2,2-dimethylcyclopropanecarboxylic acids bearing (E)- or (Z)-3-monohalovinyl side chains (haloiodo, bromo, chloro or fluoro) were synthesised and had moderate to high insecticidal activities, but these were generally lower than those of established pyrethroids with the corresponding 3-(dihalovinyl) side chains. Compounds with 3-(2-chloroprop-1-enyl) side chains were intermediate in potency between the related chrysanthemates and 3-(dichlorovinyl) esters.     

The pyrethrins and related compounds. Part XXII. Preparation of isomeric cyano-substituted 3-phenoxybenzyl esters

Preparation of 3-phenoxybenzyl chrysanthemates and their dihalovinyl analogues substituted with a cyano group at the 2-, 6-, (R)-α-, or (S)-α- positions is described. The (R)- and (S)- isomers of α-cyano-3-phenoxybenzyl esters of 2,2-difluoro-, -dichloro-, and -dibromo-vinyl analogues of cis- and trans- chrysanthemic acid are separated chromatographically, as are the separate pairs of enantiomers of fenvalerate, (RS)-α- cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate. An optically active ester of α-cyano-3-phenoxybenzyl alcohol (obtained using D -oxynitrilase) with 2,2,3,3-tetramethylcyclopropanecarboxylic acid is synthesised.     

Quantitative structure-activity relationships of pyrethroid insecticides

The structure-activity relationships of two congeneric series of pyrethroid insecticides, the methylbenzyl (1RS)-cis,trans-chrysanthemates tested against Musca domestica (houseflies) and Phaedon cochleariae (mustard beetles), and the (E)-4-aryl-3-chlorobut-2-enyl chrysanthemates and their corresponding 2,2,3,3-tetramethylcyclo-propanecarboxylates tested against M. domestica only, have been examined using multiple regression analyses and substituent constants. With M. domestica, different optimum partition values (π) were indicated for knockdown and toxicity; with P. cochleariae, an optimum π value for toxicity, similar to that for M. domestica, was obtained 24 h after application, but at later times the more lipophilic compounds were more effective. For the methylbenzyl chrysanthemates, a steric constraint associated with 3,5-dimethyl substitution reduced toxicity approximately five-fold. The influence on toxicity of geometrical isomerism and electronic effects are briefly discussed. Differences between the required polarities for knockdown and toxicity are attributed to variations in the binding affinities of pyrethroid molecules at the sites of action.     

Toxicity of some pyrethroids to the adult desert locust,Schistocerca gregaria forsk

The toxicity of a number of topically applied pyrethroids has been tested against adult male desert locusts, Schistocerca gregaria: the most potent proved to be 5-benzyl-3-furylmethyl (+)-trans-chrysanthemate (bioresmethrin) with a weighted mean LD₅₀ of 4.0 μg/g. The remaining compounds may be ranked in order of toxicity as follows: 5-benzyl-3-furylmethyl (±)-cis-trans-chrysanthemate (resmethrin) > 4-allyl-2,6-dimethyl-benzyl(+)-trans-chrysanthemate > 4-allylbenzyl (+)-trans-chrysanthemate > 2,4,6-trimethylbenzyl (+)-cis-trans-chrysanthemate > 2,3,4-trimethylbenzyl (+)-cis-trans-chrysanthemate > 2,4-dimethylbenzyl (±)-cis-trans-chrysanthemate; 2-methylbenzyl (±)-cis-trans-chrysanthemate. A small factor of synergism (4.2) was obtained with bioresmethrin following pre-treatment with sesamex, but with resmethrin the synergistic ratio (1.6) was of little practical significance.     

Insecticidal activity of the pyrethrins and related compounds V. toxicity of the methylbenzyl chrysanthemates to houseflies (Musca domestica) and mustard beetles (Phaedon cochleariae)

The insecticidal activities to houseflies and to mustard beetles of the 19 methylbenzyl (±)-cis-trans-chrysanthemates were measured to establish the patterns of substitution that produce the greatest toxicities to these insects. The two species of insect differ in their responses to the various compounds in the series. The most active compounds to houseflies and mustard beetles are, respectively, 2,4,6-and 2,3,6-trimethylbenzyl (±)-cis-trans-chrysanthemates.     

The pyrethrins and related compounds. XIII. Insecticidal methyl-, alkenyl and benzyl-substituted furfuryl and furylmethyl chrysanthemates

3-Furylmethyl and furfuryl chrysanthemates with methyl, benzyl, substituted benzyl and alkenyl substituents, and other heterocyclic analogues of these compounds, are synthesised for structure-insecticidal activity investigations.     

The pyrethrins and related compounds; Part XXIV: synthesis, 13C-nuclear magnetic resonance spectra and insecticidal activity of cycloalkyl analogues of fenvalerate

Close isosteres of fenvalerate [(RS)-α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate], in which cyclopropyl groups replace isopropyl have insecticidal activity close to or greater than the parent compounds, and diminished intravenous toxicity to rats. A direct toxicological relationship of these compounds to fenvalerate itself and to chrysanthemate esters is indicated by the consistently greater activity of esters from one of an enantiomeric pair of acids. Other esters with larger alkyl or cycloalkyl groups, or spiropentane analogues of chrysanthemates are less active insecticides. ¹³C-Nuclear magnetic resonance spectra suggest that in the α-cyanobenzyl esters there is an intramolecular through-space interaction in solution. The relationships between the chemical structures of the compounds synthesised and their relative activities to different insect species and toxicity to rats are discussed.     

Insecticidal activity of the pyrethrins and related compounds X 5-benzyl-3-furylmethyl 2,2-dimethyicyclopropanecarboxylates with ethylenic substituents at position 3 on the cyclopropane ring

The insecticidal activities against houseflies (Musca domestica L.) and mustard beetles (Phaedon cochleariae Fab.) of the chrysanthemate bioresmethrin, and of 31 related 5-benzyl-3-furylmethyl 2,2-dimethylcyclopropanecarboxylates with alkenyl, alkadienyl or alkoxycarbonylalkenyl substituents at position 3 of the cyclopropane ring are compared to determine the relative influence of the isobutenyl sidechain (as in chrysanthemates) and of the other side chains. Several substituents, in particular (E)- or (Z)-butadienyl or -pentadienyl, give considerably greater activity than isobutenyl but alkoxycarbonyl compounds are less potent.     

Insecticidal activity of the pyrethrins and related compounds: III.—Penetration of pyrethroid insecticides into mustard beetles (Phaedon cochleariae)

Substituted benzyl chrysanthemates are lost from the surface of Phaedon cochleariae Fab. at rates correlated with their toxicities to this insect, less toxic compounds in general being lost faster. The forms of the penetration curves are explained by a model system in which movement into the insect is eventually balanced by detoxification, and relative detoxification rates for the members of the series of compounds are deduced from this model. Such values assist interpretation of relations between structure and activity by indicating to what extent susceptibility to detoxification limits the potency of the less toxic compounds.     

Substrate-specificity and toxicological significance of pyrethroid-hydrolyzing esterases of mouse liver microsomes

An esterase or esterases in acetone powder preparations of mouse liver microsomes hydrolyze the cyclopropanecarboxylate ester linkage of pyrethroid insecticide chemicals derived from primary alcohols. The rate of cleavage of (+)-trans-chrysanthemates with various alcohol moieties decreases in the following order: 5-propargyl-2-furylmethyl; 5-benzyl-3-furylmethyl (bioresmethrin); 3-phenoxybenzyl; tetrahydrophthalimidomethyl esters. The hydrolysis rate of benzylfurylmethyl esters with various acid moieties decreases in the order: (+)- or (?)-trans-chrysanthemate; (+)-trans-ethanochrysanthemate; tetramethylcyclopropanecarboxylate; (+)- or (?)-cis-chrysanthemate or (+)-cis-ethanochrysanthemate. The trans-isomers of chrysanthemates and ethanochrysanthemates are hydrolyzed from 2.6- to more than 50-fold more rapidly than the corresponding cis-isomers. This enzyme system does not hydrolyze secondary alcohol esters, i.e., allethronyl (+)-trans- and (+)-cis-chrysanthemates.On intraperitoneal administration to mice, the (+)-trans-chrysanthemate and -ethanochrysanthemate of benzylfurylmethanol are of very low toxicity relative to the corresponding (+)-cis-isomers and the tetramethylcyclopropanecarboxylate. S,S,S-tributyl phosphorotrithioate (DEF) pretreatment increases the toxicity of these five compounds by 2.6- to more than 188-fold, with the exception of bioresmethrin whose toxicity is not altered. When the toxicity is increased, it is probably the result of esterase inhibition since DEF strongly inhibits the esterase activity of fresh liver microsomes while the mixed-function oxidase system remains active. The oxidase system metabolizes the chrysanthemates more rapidly than the ethanochrysanthemates of benzylfuryl-methanol. Depending upon the pyrethroid involved, the esterase or the mixed-function oxidase system, or both may be responsible for limiting the toxicity of these pyrethroids to mice.     

Insecticidal activity of the pyrethrins and related compounds. VI. Methyl-, alkenyl-, and Benzyl-furfuryl and −3-furylmethyl chrysanthemates

The influence of the nature, number and relative dispositions of substituents on the furan ring of furfuryl and 3-furylmethy chrysanthemates on insecticidal activity to two insect species is described. 5-Benzyl-3-furylmethyl chrysanthemate was the most active compound developed in the investigation.     

Effects of alcohols,glycols and monodisperse ethoxylated alcohols on mobility of 2,4-D in isolated plant cuticles

Effects of n-alcohols, ethoxylated alcohols and glycols on mobility of 2,4-dichlorophenoxy acetic acid (2,4-D) in cuticular membranes (CM) isolated from bitter orange (Citrus aurantium L.) leaves were studied. 1-Heptanol, 1-octanol and 1-nonanol had the highest effects, as they increased solute (2,4-D) mobility by 25- to 30-fold. Increasing the number of carbon atoms in the alcohols decreased their effectiveness. Ethoxylation of alcohols did not increase 2,4-D mobility and effectiveness decreased with increasing ethoxylation. Free glycols had no effect on solute mobility in isolated cuticles. The results show that ethoxylation is not required for increasing solute mobility in cuticles. It is suggested that alcohols and ethoxylated alcohols are sorbed in cuticular waxes and plasticize them. The data show that alcohols and ethoxylated alcohols having between seven and ten carbon atoms are powerful accelerator adjuvants, as long as the degree of ethoxylation is not too high. Free short-chain alcohols synthesized by leaves may act as endogenous plasticizers and modulate permeabilities of cuticles, depending on environmental and growing conditions.     

Non-Host Volatiles Disrupt the Response of the Stenographer Bark Beetle, Ips sexdentatus (Coleoptera: Scolytidae), to Pheromone-Baited traps and Maritime Pine Logs

Non-host volatiles (NHV) were tested on antennae of Ips sexdentatus with coupled gas chromatographic-electroantennographic detection (GC-EAD). Significant antennal responses were found to aggregation pheromone components, ipsdienol and amitinol, an attraction inhibitor, verbenone, and non-host bark volatiles extracted from Betula pendula, including trans-conophthorin (tC) and alcohols. The tC, a blend of three green leaf alcohols (C6-alcohols), and a blend of two bark alcohols (C8-alcohols) were tested in combination for their ability to disrupt the attraction of the stenographer bark beetle to pheromone-baited traps, unbaited and pheromone-baited maritime pine logs. The strongest disruptive effect resulted from the addition of the tC combined with the blends of NHV alcohols at high release rate, achieving an 83% reduction in trap catches, 89% reduction of attacks on unbaited pine logs, and 60% on baited logs. It is proposed that the two types of NHV have an additive effect, tC playing a major role in pheromone disruption while the alcohols would interrupt host specific signals. The results suggest that I. sexdentatus uses both bark and green leaf volatiles from non-host tree species in the host selection process. These NHV are promising disruptants, which could be used to prevent stenographer bark beetle attacks on log piles or standing trees in forest. A mixture of conifers and broad-leaved species would also disturb olfactory guided host selection supporting the assumption that more diverse forests are less prone to pest insect outbreaks.     

The degradation of (Z)- and (E)-1,3-dichloropropenes and 1,2-dichloropropane in soil

The degradation in soil of the major constituents of a 1,3-dichloropropene-1,2-dich-loropropane nematicide has been studied under laboratory and outdoor conditions. In sealed glass containers, ( Z)- and ( E)-1,3-dichloropene- 2-¹⁴C were converted in soil into the corresponding 3-chloroallyl alcohols and these alcohols were in part strongly bound to the soil. The ( Z)- and ( E)-3-chloroacrylic acids were also found as minor products. More polar products were detected and these released the chloroacrylic acids in 20–30% yield upon hydrolysis. Although the 1,3-dichloropropenes were lost by volatilisation from soil stored in open glass jars outdoors, they also underwent degradation to the same products that were detected in sealed containers. There was evidence of only slight degradation of 1,2-dichloropropane- 2-¹⁴C (4 % or less of the applied radioactivity remained unextracted from a loam soil after 5 months). When soil treated with the 1,2-dichloropropane was stored outdoors in an open glass container, less than 1 % of the original radiolabel remained in the soil after 10 days under these conditions due to volatilisation of the applied material. In a separate experiment potatoes were grown in soil 6 months after treatment with a mixture of both ( Z)- and ( E)-1,3-dichloropropene- 2-¹⁴C and 1,2-dichloropropane- 2-¹⁴C. Although 5 % of the applied radiolabel remained in the soil at potato harvest the potato tubers contained only a very small residue (0.007 mg/kg).     

The pyrethrins and related compounds part XXXIX— structure-activity relationships of pyrethroidal esters with cyclic side chains in the alcohol component against resistant strains of housefly (Musca domestica)

Activities of a range of pyrethroidal esters, incorporating structural variations in all regions of the acid and alcohol components, have been measured against two fully characterised and homozygous resistant strains of Musca domestica L. (kdr and super-kdr). The results, limited in this paper to esters of alcohols with cyclic side chains, indicate uniform resistance to the kdr strain across the whole range of structural variations. Against the super-kdr strain, while variation in the acid component has little effect, the resistance factor is sensitive to the nature of the alcohol component, in particular on whether it contains an α-cyano substituent.     

The pyrethrins and related compounds part XL— structure-activity relationships of pyrethroidal esters with acyclic side chains in the alcohol component against resistant strains of housefly (Musca domestica)

Activities of a range of pyrethroidal esters, incorporating structural variations in all regions of the acid and alcohol components, have been measured against two fully characterised and homozygous resistant strains of Musca domestica (kdr and super-kdr). The results, limited in this paper to esters of alcohols with acyclic side chains, show the same level of uniform resistance as the kdr strain observed previously, across a range of acid and alcohol variations. Against the super-kdr strain, in contrast to the cyclic side chain set, resistance factors are barely higher than for the kdr strain. Against super-kdr flies, some dependence of resistance factor on the position of the side chain substituent was detected. Polyfluorobenzyl esters confer particularly low resistance factors.     

Transformation rate of 1,3-dichloropropene and 3-chloroallyl alcohol in topsoil and subsoil material of flower-bulb fields

The extent of the risk of (Z)- and (E)-1,3-dichloropropene and their transformation products (Z)- and (E)-3-chloroallyl alcohol causing a hazard to the quality of groundwater pumped up for public water supply from below flower-bulb fields has been evaluated. The 1,3-dichloropropenes were incubated at 10°C in water-saturated subsoil material from three such fields. A first stage with gradual transformation was followed by a second stage with comparatively rapid transformation and after three months negligible amounts remained. The 3-chloroallyl alcohols were incubated at 15°C in soils from the root zone of the same fields. Complete transformation had occurred in about a week or even less. The 3-chloroallyl alcohols were also incubated in the water-saturated subsoil material at 10°C. Again, a first stage with gradual transformation was followed by a second stage with fast transformation. In most instances, the concentrations had fallen to a very low level within three months. It was concluded that it is unlikely that residues in the upper groundwater would permeate into the deeper groundwater pumped up for public water supply.     

Insecticidal activity of the pyrethrins and related compounds. VII. Insecticidal dihalovinyl analogues of cis and trans chrysanthemates

Eighteen esters of resolved cis- and trans-3-(2,2-difluoro, -dichloro or -dibromovinyl)-2,2-dimethylcyclopropanecarboxylic acids with 5-benzyl-3-furylmethyl, 3-phenoxybenzyl and α-cyano-3-phenoxybenzyl alcohols were prepared and evaluated for insecticidal activity against Musca domestica L. and Phaedon cochleariae Fab. Chlorine and bromine substituted esters are more active, in general, than those with fluorine, and in the most active esters, the cis isomer is more effective than the trans.     

Preparation of Novel Hexythiazox Analogues

Novel analogues of the title compound were prepared in several steps: via addition of methylmagnesium iodide to an acetamide derivative to yield diastereomeric amino alcohols, followed by hydrolysis, cyclization to the corresponding oxazole or thiazole derivative, and a coupling reaction with isocyanates. Results from acaricidal tests showed the compounds to be 100 times less active than hexythiazox. © 1997 SCI.