Patent Application
20220304307
The subject matter described herein is directed to arthropod repellent compounds and synergistic compositions, particularly those based on acids of pyrethroids.
Biting insects are a nuisance and are also known to be carriers of disease. Compositions that repel insects, particularly insect pests such as mosquitoes, flies and fleas, are widely used to prevent animals from being bitten by such insects. The importance of preventing biting is essentially two-fold. Firstly, there are a number of insects which are capable of infecting animals with disease causing parasites, an example being the transmission of Plasmodium falciparum by mosquitoes to cause malaria. Secondly, in many cases whether disease is transmitted or not, the bite can be extremely irritating.
Insect repellents that act to repel insects from surfaces, including the skin of animals, are commercially available. They are designed to reduce or prevent the tendency of the insect to contact the surface, thereby preventing the biting. Over the years, a number of different oils, greases, ointments, sprays, and powders have been employed as insect repellents with varying degrees of success. Other delivery methods, such as fans, heated emanators, and burning coils, have also been developed with the purpose of repelling insects. Oil of citronella was reported to be an effective insect repellent as early as 1901. Another natural product, nicotine from tobacco, was used as a repellent as long ago as 1760. Since World War II, a number of synthetic insect repellents have been introduced.
One such repellent is N,N-diethyl-m-toluamide (DEET). It is a synthetic insect repellent that has demonstrated superior insect repellency in comparison to other repellents, including natural insect repellents. However, there is concern that repeated DEET exposure may have harmful consequences. For example, possible DEET side effects are irritability, confusion, insomnia, and even seizures. For these reasons, caution is generally recommended with regard to the use of DEET as an insect repellent. This is especially true when DEET is applied to children, who are more susceptible to the potentially injurious effects of exposure to DEET.
Pyrethrins, which are cyclopropanecarboxylates, the naturally occurring extracts from the blossoms of pyrethrum flowers (Chrysanthemum cinerariae-folium) grown mainly in East Africa, were widely used as insecticides before the advent of synthetic materials such as DDT. The pyrethrins are effective in killing a wide range of insect species, and they also function as insect repellents [Burden, Pest Control, 43, 16 (1975)]. Although they display relatively low toxicity toward mammals and do not leave harmful residues, they undergo rapid biodegradation, they have poor photooxidative stability, their availability is uncertain, and it is costly to extract and process them.
Efforts have been underway to produce synthetic cyclopropanecarboxylate insecticides, pyrethroids, which would overcome these disadvantages. Pyrethroids are known to have significant insecticidal effects and are effective in repelling and/or killing blood sucking insects. 5-Benzyl-3-furylmethyl chrysanthemate (resmethrin) [Elliott, et al., Nature, 213, 493 (1967)], a powerful contact insecticide, was an early success. A notable result of these efforts was the discovery of the pyrethroid, 3-phenoxybenzyl 3-(β,β-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (permethrin), having the combination of toxicity and knockdown attributes of the natural pyrethrins and resmethrin together with a previously unattained level of photooxidative stability [Elliott, et al., Nature, 246, 169 (1973); S. African Patent 73/3528]. Subsequently, permethrin was determined to be the best insect repellent for clothing and field treatment of U.S. military combat uniforms, and has been used as the standard repellent treatment of uniforms since 1991 (Armed Forces Pest Management Board Technical Guide No. 36, Personal Protective Measures against Insects and other Arthropods of Military Significance).
Of course, the repellent treatment will need to be re-applied. For economic and safety reasons, it would be beneficial to be able to use the least amount of active agents that provide the desired efficacy. The same is true for spatial repellents, vapor-active and deployed to keep a room, house, or tent, free of biting insects. Therefore, what is needed are highly efficacious compounds, especially those that can synergize with other compounds, whereby the concentrations and amounts of compounds required for efficacy is lessened. The subject matter described herein addresses the shortcomings of the art.
In certain embodiments, the subject matter described herein is directed to a compound of Formula I
wherein R1 and R2 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, haloaryl, C6-C12 heteroaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R1 and R2 are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R3 and R4 are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R5 is selected from the group consisting of linear or branched C5-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C5 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl; and
X is selected from the group consisting of O, NH, and S.
In certain embodiments, the subject matter described herein is directed to a composition comprising a compound of Formula II′ or a compound of Formula III′:
where R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl, and
a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1,
wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter described herein is directed to a composition comprising a compound of Formula IV, a compound of Formula V, or a compound of Formula VI:
wherein Y is selected from the group consisting of O, NH, and S;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
a compound of Formula II′ or a compound of Formula III′:
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter described herein is directed to a composition comprising a compound of Formula VII
wherein R28 is selected from the group consisting of hydrogen, haloalkyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl, cyano, hydroxy, and
a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, VUAA-1, nootkatone, a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, the subject matter described herein is directed to a composition comprising a compound of Formula I′ and a compound of Formula II′ or a compound of Formula III′, wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula II′ or a compound of Formula III′ and a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, nootkatone, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula IV, a compound of Formula V, or a compound of Formula VI and a compound of Formula II′ or a compound of Formula III′, wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula VII and a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, nootkatone, VUAA-1 a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI, wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula I′ and a compound of Formula II′ or a compound of Formula III′, wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter disclosed herein is directed to a method for controlling one or more arthropods, comprising contacting the one or more arthropods with a synergistic composition comprising a compound of Formula II′ or a compound of Formula III′ and a pyrethroid, wherein the synergistic composition produces, when the one or more arthropods are brought into contact with the synergistic composition, a combined toxicant effect greater than the sum of the separate toxicant effects from the compound of Formula II′ or Formula III′ and the pyrethroid, at comparable concentrations.
In certain embodiments, the subject matter disclosed herein is directed to a method for controlling one or more arthropods, comprising exposing said one or more arthropods to a synergistic composition comprising a compound of Formula II′ or a compound of Formula III′ and a pyrethroid, wherein the synergistic composition produces, when said one or more arthropods are exposed to the synergistic composition, a combined toxicant effect greater than the sum of the separate toxicant effects from the compound of Formula II′ or Formula III′ and the pyrethroid, at comparable concentrations.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a carrier and a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, or Formula VII
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6 and R7 are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C2 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, halo, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
R11 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, cycloalkyl, halo, haloalkyl, alkenyl, alkynyl, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, alkoxy, halo, haloalkyl, alkenyl, alkynyl, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy.
In certain embodiments, the subject matter described herein is directed to a composition comprising an essential oil and a compound selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, and Formula VII, wherein the composition is synergistic, in admixture with a carrier.
In certain embodiments, the subject matter described herein is directed to a method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising an essential oil, and a second compound selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, and Formula VII, wherein the composition is synergistic, in admixture with a carrier.
Other embodiments are also described.
Described herein are compounds, compositions, and methods that provide desired insect repellency. The compositions comprise acids, esters, aldehydes, amides, oximes, sulfamides, sulfonamides, or alcohols of pyrethroid-type compounds. The compounds demonstrate excellent repellency both alone and in synergistic compositions with other compounds. In certain embodiments, the pyrethroid-type compounds can also synergize the toxicity of pyrethroids, thereby more effectively controlling insects.
Pyrethroids typically contain ester linkages (Table 1-1). Carboxylesterase hydrolysis of pyrethroids is considered a detoxication reaction that will produce a pyrethroid acid and alcohol. Although pyrethroids such as transfluthrin and metofluthrin are often utilized in commercial repellents, it was generally accepted that the acids and alcohols of these pyrethroids were devoid of any biological activity, including repellency or toxicity. Without wishing to be bound by theory, it is understood that resistant strains of insects have up-regulated esterases as a mechanism of resistance, although binding to the esterase regardless of whether any hydrolysis occurs may be a contributing factor (K Wang, Y Huang, X Li, and M Chen, Functional Analysis of a Carboxylesterase Gene Associated With Isoprocarb and Cyhalothrin Resistance in Rhopalosiphum padi (L.). Frontiers in Physiology 9:992, 2018). As described herein, however, it has been found that pyrethroid alcohol and acids unexpectedly have repellent bioactivity. As such, the subject matter described herein is directed to methods of repelling insects using compositions comprising acids, alcohols, aldehydes, or esters of pyrethroid compounds. In certain embodiments, the repellent bioactivity of the pyrethroid-type acid, alcohol, aldehyde, or ester is greater than that of the parent pyrethroid compound. Furthermore, the methods and compositions disclosed herein are effective, even at low concentrations.
α-cyano-3-phenoxybenzyl alcohol
α-cyano-3-phenoxybenzyl alcohol
The presently disclosed subject matter will now be described more fully hereinafter. However, many modifications and other embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. In other words, the subject matter described herein covers all alternatives, modifications, and equivalents. In the event that one or more of the incorporated literature, patents, and similar materials differs from or contradicts this application, including but not limited to defined terms, term usage, described techniques, or the like, this application controls. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in this field. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.
As used in the present specification, the following words, phrases and symbols are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise.
A dash (“-”) that is not between two letters or symbols is used to indicate a point of attachment for a substituent. For example, —C(O)NH2 is attached through the carbon atom. A dash at the front or end of a chemical group is a matter of convenience; chemical groups may be depicted with or without one or more dashes without losing their ordinary meaning. A wavy line or a dashed line drawn through or perpendicular across the end of a line in a structure indicates a specified point of attachment of a group. Unless chemically or structurally required, no directionality or stereochemistry is indicated or implied by the order in which a chemical group is written or named.
The prefix “Cu-Cv” indicates that the following group has from u to v carbon atoms. For example, “C1-C6 alkyl” indicates that the alkyl group has from 1 to 6 carbon atoms.
Reference to “about” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se. In certain embodiments, the term “about” includes the indicated amount ±50%. In certain other embodiments, the term “about” includes the indicated amount ±20%. In certain other embodiments, the term “about” includes the indicated amount ±10%. In other embodiments, the term “about” includes the indicated amount ±5%. In certain other embodiments, the term “about” includes the indicated amount 1%. In certain other embodiments, the term “about” includes the indicated amount ±0.5% and in certain other embodiments, 0.1%. Such variations are appropriate to perform the disclosed methods or employ the disclosed compositions. Also, to the term “about x” includes description of “x”. Also, the singular forms “a” and “the” include plural references unless the context clearly dictates otherwise. Thus, e.g., reference to “the compound” includes a plurality of such compounds and reference to “the assay” includes reference to one or more assays and equivalents thereof known to those skilled in the art.
“Alkyl” refers to an unbranched or branched saturated hydrocarbon chain. As used herein, alkyl has 1 to 20 carbon atoms (i.e., C1-C20 alkyl), 1 to 12 carbon atoms (i.e., C1-C12 alkyl), 1 to 8 carbon atoms (i.e., C1-C8 alkyl), 1 to 6 carbon atoms (i.e., C1-C6 alkyl), 1 to 4 carbon atoms (i.e., C1-C4 alkyl), 5 to 12 carbon atoms (i.e., C5-C12), or 1 to 3 carbon atoms (i.e., C1-C3 alkyl). Examples of alkyl groups include, e.g., methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl and 3-methylpentyl. When an alkyl residue having a specific number of carbons is named by chemical name or identified by molecular formula, all positional isomers having that number of carbons may be encompassed; thus, for example, “butyl” includes n-butyl (i.e., —(CH2)3CH3), sec-butyl (i.e., —CH(CH3)CH2CH3), isobutyl (i.e., —CH2CH(CH3)2) and tert-butyl (i.e., —C(CH3)3); and “propyl” includes n-propyl (i.e., —(CH2)2CH3) and isopropyl (i.e., —CH(CH3)2).
Certain commonly used alternative chemical names may be used. For example, a divalent group such as a divalent “alkyl” group, a divalent “aryl” group, etc., may also be referred to as an “alkylene” group or an “alkylenyl” group, an “arylene” group or an “arylenyl” group, respectively. Also, unless indicated explicitly otherwise, where combinations of groups are referred to herein as one moiety, e.g., arylalkyl or aralkyl, the last mentioned group contains the atom by which the moiety is attached to the rest of the molecule.
“Alkoxy” refers to the group “alkyl-O—”. Examples of alkoxy groups include, e.g., methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy and 1,2-dimethylbutoxy.
“Amino” refers to the group —NRyRz wherein Ry and Rz are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroalkyl or heteroaryl; each of which may be optionally substituted, as defined herein.
“Aryl” refers to an aromatic carbocyclic group having a single ring (e.g., monocyclic) or multiple rings (e.g., bicyclic or tricyclic) including fused systems. As used herein, aryl has 6 to 20 ring carbon atoms (i.e., C6-C20 aryl), 6 to 12 carbon ring atoms (i.e., C6-C12 aryl), or 6 to 10 carbon ring atoms (i.e., C6-C10 aryl). Examples of aryl groups include, e.g., phenyl, naphthyl, fluorenyl and anthryl. Aryl, however, does not encompass or overlap in any way with heteroaryl defined below. If one or more aryl groups are fused with a heteroaryl, the resulting ring system is heteroaryl. If one or more aryl groups are fused with a heterocyclyl, the resulting ring system is heterocyclyl.
“Arylhalo” refers to an aryl that is substituted with one or more halo substituents. In certain embodiments, the arylhalo may be substituted with 1, 2, 3, 4, 5, or 6 halo substituents.
“Arylalkyl” or “Aralkyl” refers to the group “aryl-alkyl-”, such as benzyl.
“Cycloalkyl” refers to a saturated or partially unsaturated cyclic alkyl group having a single ring or multiple rings including fused, bridged and spiro ring systems. The term “cycloalkyl” includes cycloalkenyl groups (i.e., the cyclic group having at least one double bond) and carbocyclic fused ring systems having at least one sp3 carbon atom (i.e., at least one non-aromatic ring). As used herein, cycloalkyl has from 3 to 20 ring carbon atoms (i.e., C3-C20 cycloalkyl), 3 to 12 ring carbon atoms (i.e., C3-C12 cycloalkyl), 3 to 10 ring carbon atoms (i.e., C3-C10 cycloalkyl), 3 to 8 ring carbon atoms (i.e., C3-C8 cycloalkyl), 3 to 7 ring carbon atoms (i.e., C3-C7 cycloalkyl), or 3 to 6 ring carbon atoms (i.e., C3-C6 cycloalkyl). Monocyclic groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Polycyclic groups include, for example, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, adamantyl, norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl and the like. Further, the term cycloalkyl is intended to encompass any non-aromatic ring which may be fused to an aryl ring, regardless of the attachment to the remainder of the molecule. Still further, cycloalkyl also includes “spirocycloalkyl” when there are two positions for substitution on the same carbon atom, for example spiro[2.5]octanyl, spiro[4.5]decanyl, or spiro[5.5]undecanyl.
“Alkyl-alkoxy” refers to the group “-alkyl-alkoxy.”
“Cycloalkylalkyl” refers to the group “cycloalkyl-alkyl-”.
“Halogen” or “halo” refers to atoms occupying group VIIA of the periodic table, such as fluoro, chloro, bromo or iodo.
“Haloalkyl” refers to an unbranched or branched alkyl group as defined above, wherein one or more (e.g., 1 to 6, or 1 to 3) hydrogen atoms are replaced by a halogen. For example, where a residue is substituted with more than one halogen, it may be referred to by using a prefix corresponding to the number of halogen moieties attached. Dihaloalkyl and trihaloalkyl refer to alkyl substituted with two (“di”) or three (“tri”) halo groups, which may be, but are not necessarily, the same halogen. Examples of haloalkyl include, e.g., trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl and the like.
“Haloalkoxy” refers to an alkoxy group as defined above, wherein one or more (e.g., 1 to 6, or 1 to 3) hydrogen atoms are replaced by a halogen.
“Hydroxyalkyl” refers to an alkyl group as defined above, wherein one or more (e.g., 1 to 6, or 1 to 3) hydrogen atoms are replaced by a hydroxy group.
“Heteroaryl” refers to an aromatic group having a single ring, multiple rings or multiple fused rings, with one or more ring heteroatoms independently selected from nitrogen, oxygen, and sulfur. As used herein, heteroaryl includes 1 to 20 ring carbon atoms (i.e., C1-C20 heteroaryl), 3 to 12 ring carbon atoms (i.e., C3-C12 heteroaryl), or 3 to 8 carbon ring atoms (i.e., C3-C8 heteroaryl), and 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, oxygen and sulfur. In certain instances, heteroaryl includes 9-10 membered ring systems, 5-10 membered ring systems, 5-7 membered ring systems, or 5-6 membered ring systems, each independently having 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, oxygen and sulfur. Examples of heteroaryl groups include, e.g., acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzofuranyl, benzothiazolyl, benzothiadiazolyl, benzonaphthofuranyl, benzoxazolyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, isoquinolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, phenazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl and triazinyl. Examples of the fused-heteroaryl rings include, but are not limited to, benzo[d]thiazolyl, quinolinyl, isoquinolinyl, benzo[b]thiophenyl, indazolyl, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridinyl and imidazo[1,5-a]pyridinyl, where the heteroaryl can be bound via either ring of the fused system. Any aromatic ring, having a single or multiple fused rings, containing at least one heteroatom, is considered a heteroaryl regardless of the attachment to the remainder of the molecule (i.e., through any one of the fused rings). Heteroaryl does not encompass or overlap with aryl as defined above.
“Heteroarylalkyl” refers to the group “heteroaryl-alkyl-”.
“Heterocyclyl” refers to a saturated or partially unsaturated cyclic alkyl group, with one or more ring heteroatoms independently selected from nitrogen, oxygen and sulfur. The term “heterocyclyl” includes heterocycloalkenyl groups (i.e., the heterocyclyl group having at least one double bond), bridged-heterocyclyl groups, fused-heterocyclyl groups and spiro-heterocyclyl groups. A heterocyclyl may be a single ring or multiple rings wherein the multiple rings may be fused, bridged or spiro, and may comprise one or more (e.g., 1 to 3) oxo (═O) or N-oxide (—O−) moieties. Any non-aromatic ring containing at least one heteroatom is considered a heterocyclyl, regardless of the attachment (i.e., can be bound through a carbon atom or a heteroatom). Further, the term heterocyclyl is intended to encompass any non-aromatic ring containing at least one heteroatom, which ring may be fused to an aryl or heteroaryl ring, regardless of the attachment to the remainder of the molecule. As used herein, heterocyclyl has 2 to 20 ring carbon atoms (i.e., C2-C20 heterocyclyl), 2 to 12 ring carbon atoms (i.e., C2-C12 heterocyclyl), 2 to 10 ring carbon atoms (i.e., C2-C10 heterocyclyl), 2 to 8 ring carbon atoms (i.e., C2-C8 heterocyclyl), 3 to 12 ring carbon atoms (i.e., C3-C12 heterocyclyl), 3 to 8 ring carbon atoms (i.e., C3-C8 heterocyclyl), or 3 to 6 ring carbon atoms (i.e., C3-C6 heterocyclyl); having 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, sulfur or oxygen. When the heterocycle ring contains 4- or 6-ring atoms, it is also referred to herein as a 4- or 6-membered heterocycle. Examples of heterocyclyl groups include, e.g., azetidinyl, azepinyl, benzodioxolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzopyranyl, benzodioxinyl, benzopyranonyl, benzofuranonyl, dioxolanyl, dihydropyranyl, hydropyranyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, furanonyl, imidazolinyl, imidazolidinyl, indolinyl, indolizinyl, isoindolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, oxiranyl, oxetanyl, phenothiazinyl, phenoxazinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tetrahydropyranyl, trithianyl, tetrahydroquinolinyl, thiophenyl (i.e., thienyl), tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl and 1,1-dioxo-thiomorpholinyl. The term “heterocyclyl” also includes “spiroheterocyclyl” when there are two positions for substitution on the same carbon atom. Examples of the spiro-heterocyclyl rings include, e.g., bicyclic and tricyclic ring systems, such as 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl and 6-oxa-1-azaspiro[3.3]heptanyl. Examples of the fused-heterocyclyl rings include, but are not limited to, 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridinyl, indolinyl and isoindolinyl, where the heterocyclyl can be bound via either ring of the fused system.
“Heterocyclylalkyl” refers to the group “heterocyclyl-alkyl-.”
“Sulfonyl” refers to the group —S(O)2Ry, where Ry is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroalkyl or heteroaryl; each of which may be optionally substituted, as defined herein. Examples of sulfonyl are methylsulfonyl, ethylsulfonyl, phenylsulfonyl and toluenesulfonyl.
The compounds of the invention, or their agrochemically acceptable salts include an asymmetric center and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)- or, as (D)- or (L)- for amino acids. The present invention is meant to include all such possible isomers, as well as their racemic, optically pure, and enantiomerically/diastereomerically enriched forms. Optically active (+) and (−), (R)- and (S)-, or (D)- and (L)-isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques, for example, chromatography and fractional crystallization. Conventional techniques for the preparation/isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC). When the compounds described herein contain olefinic double bonds or other centres of geometric asymmetry, and unless specified otherwise, it is intended that the compounds include both E and Z geometric isomers.
A “stereoisomer” refers to a compound made up of the same atoms bonded by the same bonds but having different three-dimensional structures, which are not interchangeable. The present invention contemplates various stereoisomers and mixtures thereof and includes “enantiomers,” which refers to two stereoisomers whose molecules are nonsuperimposeable mirror images of one another.
“Diastereomers” are stereoisomers that have at least two asymmetric atoms, but which are not mirror-images of each other.
Relative centers of the compounds as depicted herein are indicated graphically using the “thick bond” style (bold or parallel lines) and absolute stereochemistry is depicted using wedge bonds (bold or parallel lines).
As used herein, “OR” refers to the Orlando insecticide-susceptible strain of Ae. aegypti.
As used herein, “PR” refers to the pyrethroid-resistant Puerto Rico (PR) strain of Ae. aegypti.
As used herein, “pyrethrum,” or “natural pyrethrins” refers to a botanical mixture of naturally derived insecticides commonly used in insect control. It is a mixture of six closely related chemical forms extracted from the Chrysanthemum plant (Pyrethrin I, Cinerin I, Jasmolin I, Pyrethrin II, Cinerin II, and Jasmolin II).
Additional definitions may also be provided below as appropriate.
In certain embodiments, the subject matter described herein is directed to compounds of Formula I:
wherein R1 and R2 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, C6-C12 aryl, haloaryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R1 and R2 are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R3 and R4 are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R5 is selected from the group consisting of linear or branched C5-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C5 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl; and
X is selected from the group consisting of O, NH, and S.
In certain embodiments, R3 and R4 are each C1-C3 alkyl.
In certain embodiments, R3 and R4 are each methyl.
In certain embodiments, R1 and R2 are each halo.
In certain embodiments, R1 and R2 are each independently selected from chloro, bromo, and fluoro.
In certain embodiments, R1 and R2 are each independently chloro.
In certain embodiments, X is O.
In certain embodiments, X in NH.
In certain embodiments, R5 is selected from the group consisting of linear C5-C12 alkyl, haloalkyl, and C3-C5 cycloalkyl.
In certain embodiments, R5 is selected from the group consisting of pentyl, trifluoroethyl, cyclobutyl, cyclopentyl, and cyclopropyl.
In certain embodiments, the compound of Formula I is selected from the group consisting of:
In certain embodiments, the subject matter described herein is directed to compounds of Formula II:
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6 and R7 are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl; and
In certain embodiments, X is O.
In certain embodiments, R10 is selected from hydrogen, haloalkyl, alkenyl, alkynyl, C1-C12 alkyl, or C3-C12 cycloalkyl.
In certain embodiments, R8 and R9 are each methyl.
In certain embodiments, R6 and R7 are each independently selected from halo or C1-C3 alkyl.
In certain embodiments, the compound of Formula II is selected from the group consisting of:
In certain embodiments, the subject matter described herein is directed to compounds of Formula III
wherein R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
In certain embodiments, R21, R22, R23, R24, and R25 are each independently selected from hydrogen and halo.
In certain embodiments, R23 is halo. In certain embodiments, R23 is chloro.
In certain embodiments, R21, R22, R24, and R25 are each hydrogen.
In certain embodiments, P is O.
In certain embodiments, R26 is branched C1-C6 alkyl. In certain embodiments, R26 is isopropyl.
In certain embodiments, R27 is hydrogen.
In certain embodiments, the compound of Formula III is
In certain embodiments, the subject matter described herein is directed to compounds of Formula IV:
wherein Y is selected from the group consisting of O, NH, and S; and
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
In certain embodiments, Y is O.
In certain embodiments, R11 is CN.
In certain embodiments, the compound of Formula IV is
In certain embodiments, R11 is H.
In certain embodiments, the compound of Formula IV is
In certain embodiments, the subject matter described herein is directed to compounds of Formula V:
wherein R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
In certain embodiments, X1 is O.
In certain embodiments, the double bond between X2 and X3 is present, wherein X3 is C (with —COH attached), and X2 is CH.
In certain embodiments, R19 is benzyl.
In certain embodiments, the compound of Formula V is
In certain embodiments, X2 is N, which is substituted by —COH.
In certain embodiments, X1 and X3 are each C═O, wherein the double bond between X2 and X3 is absent.
In certain embodiments, R19 and R20 are taken together with the carbon to which each is attached to form a cyclohexyl ring.
In certain embodiments, the compound of Formula V is
In certain embodiments, the subject matter described herein is directed to compounds of Formula VI:
wherein R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy; and
R18 is selected from the group consisting of hydrogen, haloalkyl, and linear or branched C1-C6 alkyl.
In certain embodiments, R18 is hydrogen.
In certain embodiments R13, R14, R16, and R17 are each halo. In certain embodiments R13, R14, R16, and R17 are each fluoro.
In certain embodiments, R15 is hydrogen. In certain embodiments, R15 is alkyl-alkoxy.
In certain embodiments, the compound of Formula VI is selected from
In certain embodiments, the subject matter described herein is directed to compounds of Formula VII:
wherein R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy; and
wherein M is selected from the group consisting of O, NH, and S; and
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, and hydroxy.
In certain embodiments, R30, R31, R32, and R34 are each hydrogen.
In certain embodiments, R33 is
In certain embodiments, R40, R41, R42, R43, and R44 are each hydrogen.
In certain embodiments, M is O.
In certain embodiments, R28 is hydrogen.
In certain embodiments, the compound of Formula VII is
In certain embodiments, R30, R31, R32, R33, and R34 are each hydrogen.
In certain embodiments, the subject matter disclosed herein is directed to compounds of Formula I′:
wherein R1′ and R2′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R1′ and R2′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R3′ and R4′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R5′ is selected from the group consisting of linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl; and
X′ is selected from the group consisting of O, NH, and S.
In certain embodiments, X′ is O.
In certain embodiments, R3′ and R4′ are each methyl.
In certain embodiments, R5′ is linear or branched C1-C6 alkyl.
In certain embodiments, the subject matter disclosed herein is directed to compounds of Formula II′:
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl; and
X″ is selected from the group consisting of O, NH, and S.
In certain embodiments, X″ is O.
In certain embodiments, R6′ and R7′ are each independently selected from halo or C1-C6 alkyl.
In certain embodiments, R6′ and R7′ are each halo. In certain embodiments, R6′ and R7′ are each chloro.
In certain embodiments, R8′ and R9′ are each methyl.
In certain embodiments, the compound of Formula II is
In certain embodiments, the subject matter disclosed herein is directed to compounds of Formula III′:
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S; and
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl.
In certain embodiments, P′ is O.
In certain embodiments, R23′ is halo. In certain embodiments, R23′ is chloro.
In certain embodiments, R21′, R22′, R24′, and R25′ are each hydrogen.
In certain embodiments, R26′ is branched C1-C6 alkyl. In certain embodiments, R26′ is isopropyl.
In certain embodiments, R27′ is hydrogen.
In certain embodiments, the compound of Formula III′ is
The repellent compositions described herein may take various forms, including solutions, dusts, granular formulations, and emulsions. They may be prepared from concentrates, such as emulsifiable concentrates and wettable powders. In addition to the active agents, the compositions can also comprise various inert ingredients, depending upon the form taken by the composition.
If prepared from an emulsifiable concentrate, the composition may contain a surfactant such as, for example, a mixture of a polyethylene oxide with a blend of oil soluble non-ionic and anionic sulfonates. The surfactant normally comprises between about 1 and 15% by weight of the emulsifiable concentrate.
Wettable powders can also be used to make the repellent compositions. Compositions so made may be applied to the area to be protected as emulsions in water or other liquid diluents. Typical among the carriers employed in wettable powders are walnut flour, cane sugar, fuller's earth, attapulgite clays, kaolin clays, silicas and other highly absorbent, readily wetted carriers. The wettable powders themselves generally are prepared to contain about 5 to 80% by weight of the active component, depending on the absorbency of the carrier. A wettable powder usually also contains a small amount of a surfactant.
Granular repellent compositions, wherein the active component is carried on relatively coarse particles as the carrier, are also useful in repelling crawling insect pests. Dry dusts, in which the active component is admixed with finely divided solids such as talc, attapulgite clay, kieselguhr, and other organic and inorganic solids, which act as carriers for the active component, also find utility. These finely divided solids usually have an average particle size of less than about 50 microns.
Pressurized sprays such as aerosols, in which the active component is present in solution or in a finely divided form, may also be used.
The concentration of the active agent(s) in any of the repellent compositions may vary in the range from about 0.00001% to about 10% by weight, depending on the formulation. A very broad latitude in the type of repellent composition and the concentration of the active agent(s) within the aforesaid range is possible.
In certain embodiments, the compositions described herein comprise two or more compounds or active agents wherein the combination of the two or more compounds or active agents is synergistic. In certain embodiments, the two or more compounds or active agents each independently have a concentration of about 0.1, 1.0, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 800, or 1000 μg/cm2.
In certain embodiments, the subject matter disclosed herein is directed to a compound of Formula I, in intimate admixture with a carrier.
In certain embodiments, the compositions disclosed herein comprise a compound of Formula I and a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, wherein the composition is synergistic, in intimate admixture with a carrier, in any molar or weight ratio.
In certain embodiments, the compositions disclosed herein comprise about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50% of a compound of Formula II or Formula III and 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50% of a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, wherein the composition is synergistic, in intimate admixture with a carrier. In certain embodiments, the compound of Formula II or Formula III comprises about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 2%5, 30%, 40%, 50%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, or 98% of the composition in combination with a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, and VUAA-1, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, the compositions disclosed herein comprise a compound of Formula II or Formula III and a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, wherein the composition is synergistic, in intimate admixture with a carrier, in any molar or weight ratio.
In certain embodiments, the compositions disclosed herein comprise about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50% of a compound of Formula II′ or Formula III′ and 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50% of a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, and VUAA-1, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, the compound of Formula II′ or Formula III′ comprises about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 2%5, 30%, 40%, 50%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97% or 98% of the composition in combination with a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, in intimate admixture with a carrier.
In certain embodiments, the compositions disclosed herein comprise a compound of Formula II′ or a compound of Formula III′ a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, and VUAA-1, wherein the composition is synergistic, in intimate admixture with a carrier, in any weight or molar ratio.
In certain embodiments, the compositions disclosed herein comprise about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50% of a compound of Formula IV, Formula V, or Formula VI, and 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50% of a compound of Formula II′ or Formula III′, wherein the composition is synergistic, in intimate admixture with a carrier. In certain embodiments, the compound of Formula IV, Formula V, or Formula VI comprises about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 2%5, 30%, 40%, 50%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, 97%, or 98% of the composition in combination with a compound of Formula II′ or Formula III′, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, the compositions disclosed herein comprise a compound of Formula IV, Formula V, or Formula VI, and a compound of Formula II′ or Formula III′, wherein the composition is synergistic, in intimate admixture with a carrier, in any weight or molar ratio.
In certain embodiments, the compositions disclosed herein comprise about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50% of a compound of Formula VII and about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50% of a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI, wherein the composition is synergistic, in intimate admixture with a carrier. In certain embodiments, the compound of Formula VII comprises about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 2%5, 30%, 40%, 50%, 60%, 65%, 70%, 75%, 80%0, 90%, 95%, 96%, or 98% of the composition in combination with a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, and VUAA-la compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI.
In certain embodiments, the compositions disclosed herein comprise a compound of Formula VII and a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI, wherein the composition is synergistic, in intimate admixture with a carrier, in any molar or weight ratio.
In certain embodiments, the compositions disclosed herein comprise about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50% of a compound of Formula I′ and about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50% of a compound of Formula II′ or Formula III′, wherein the composition is synergistic, in intimate admixture with a carrier. In certain embodiments, the compound of Formula I′ comprises about 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 2%5, 30%, 40%, 50%, 60%, 65%, 70%, 75%, 80%, 90%, 95%, 96%, or 98% of the composition in combination with a compound of Formula II′ or III′, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, the compositions disclosed herein comprise a compound of Formula I′ and a compound of Formula II′ or Formula III′, wherein the composition is synergistic, in intimate admixture with a carrier, in any molar or weight ratio.
In certain embodiments, the compositions disclosed herein comprise two compounds of Formula II, two compounds of Formula III, or one compound of Formula II and one compound of Formula III, and a carrier, wherein the composition is synergistic.
In certain embodiments, the compositions disclosed herein comprise about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50% of an essential oil; and about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50% of a compound selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, and Formula VII, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, the compositions disclosed herein comprise an essential oil and a compound selected from the group consisting of a pyrethroid, a compound of Formula II, a compound of Formula III, a compound of Formula IV, a compound of Formula V, a compound of Formula VI, and a compound of Formula VII, wherein the composition is synergistic, in intimate admixture with a carrier, in any molar or weight ratio. In certain embodiments of this embodiment, the essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, and tea tree oil. In certain embodiments of this embodiment, the essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, Canadian balsam, nutmeg oil, fennel oil, dill weed oil, balsam copaiba, and tea tree oil. In certain embodiments of this embodiment, wherein said second compound is a pyrethroid, said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, empenthrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin. In certain embodiments of this embodiment, wherein said second compound is a pyrethroid, said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
In certain embodiments, the subject matter disclosed herein is directed to a composition comprising about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50%, of a compound of Formula II, a compound of Formula II′, a compound of Formula III′, or a compound of Formula III; and about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50% of a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, wherein the composition is synergistic, in intimate admixture with a carrier.
“Synergistic” as used herein refers to a combination which is more effective than the additive effects of the two or more single agents. A determination of a synergistic interaction between two active compounds may, in some embodiments, be based on the results obtained from the experimental information described herein. The results of these experiments can be analyzed using, for example, the Bliss activity method or co-toxicity factors (CF), described further herein.
In certain embodiments, the subject matter described herein is directed to a method of repelling an arthropod from an object or locus, comprising contacting said object or locus with any compound or composition disclosed herein. In certain embodiments, the arthropod is repelled from an adjacent area to said locus. In embodiments, the arthropod is not physically contacted with said object or locus.
In certain embodiments, the subject matter described herein is directed to a method of repelling arthropods, comprising contacting an object or locus with any compound or composition disclosed herein, wherein the arthropods are repelled from an adjacent area to said object or locus, wherein the arthropods are not physically contacted with the object or locus.
In certain embodiments, the subject matter described herein is directed to a method of providing any compound or composition disclosed herein in an arthropod repellent medium from which a vaporized compound or composition disclosed herein can be dispersed. Non-limiting examples of suitable media include alcohols such as ethanol, glycerin and polyethylene glycol; ketones such as acetone; ethers such as tetrahydrofuran and dioxane; aliphatic hydrocarbons or petroleum distillates such as gasoline, naphtha, mineral spirits, tar, hexane, kerosene, toluene, xylene, limonene, turpentine, paraffin and petroleum benzene; esters such as ethyl acetate; and essential oils such as pine oil or citronella oil,
In certain embodiments, vaporization of the repellent may be assisted by thermal volatilization. Thermal volatilization may proceed by flame, ionizing radiation, oven, sunlight, electrical pulse, laser, gas heating element, or electric-powered heating element, such as induction heating, chemical reaction, microwave irradiation, ultrasound or a mixture thereof.
In certain embodiments, the compositions or compounds disclosed herein can formulated for use in a vaporizer, evaporator, fan, heat, candle, or wicked apparatus.
The spatial arthropod repellent compounds disclosed herein may be formulated into any suitable composition to dispense a suitable amount of the repellent compound into an environmental area in which it is desired to repel arthropods, wherein the arthropods do not come into contact with the locus. This repellency effective amount would typically range from about 1 mg/cm2 down to about 1 μg/cm2 or from about 100 g/cm2 down to about 30 ng/cm2 of the base area of the environmental area in which repellency is to be sought. In certain embodiments, the spatial arthropod repellent compounds disclosed herein may be formulated into any suitable composition to dispense a suitable amount of the repellent compound onto a locus, wherein the insects are repelled at least 1 cm, 2 cm, 1 in, 2 in, 3 in, 4 in, 5 in, 6 in, 7 in, 8 in, 9 in, 10 in, 11 in, 1 foot, 2 feet, 3 feet, 4 feet, 5 feet, 6 feet, 7 feet, 8 feet, 9 feet, 10 feet, 11 feet, 12 feet, 13 feet, 14 feet, 15 feet, 16 feet, 17 feet, 18 feet, 19 feet, 20 feet, 21 feet, 22 feet, 23 feet, 24 feet, or 25 feet from the locus. In certain embodiments, arthropod repellent compounds disclosed herein are effective both in the vapor phase as spatial repellents and on contact.
In certain embodiments, the subject matter disclosed herein is directed to methods for repelling one or more insects using the compositions described herein.
In repelling insect pests according to the methods, the locus from which such insect pests are to be repelled will be contacted with a repellent amount of the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula I′, Formula II′, Formula III′, or a synergistic composition. A repellent amount of the compound of Formula I Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula I′, Formula II′, Formula III′, or a synergistic composition can vary somewhat, depending on the species of insect to be repelled, the nature of the locus, including the type of surface, from which the insects are to be repelled, and so forth, but generally between about 1 mg/m2 and 200 mg/m2 is a repellent amount. As is well known in the art, the degree of effectiveness of the repellent may vary with the formulation and the method of application.
In carrying out the methods, the compound of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula I′, Formula II′, Formula III′, or a synergistic composition may be applied in any suitable fashion to the area in which the repellency of insect pests, including acarids, is desired. Means of effective applications are well known in the art.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula II′ or a compound of Formula III′ in an amount of about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50%; and a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1 in an amount of about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50%, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, in the above method, the composition contains about 0.0001 to 999,999, 0.0001 to 100,000, 0.001 to 1, 0.05 to 100, 10 to 300, 60 to 700, 50 to 75, 25 to 100, 2 to 10, 100 to 500, or 300 to 1000, 800 to 10,000 parts per million of a compound of Formula II′ or a compound of Formula III′.
In certain embodiments of the methods described herein, the compositions comprise two or more compounds or active agents wherein the combination of the two or more compounds or active agents is synergistic. In certain embodiments, the two or more compounds or active agents each independently have a concentration of about 0.1, 1.0, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 800, or 1000 μg/cm2.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula IV, a compound of Formula V, or a compound of Formula VI in an amount of about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50%; and a compound of Formula II′ or a compound of Formula III′ in an amount of about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50%, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, in the above method, the composition contains about 0.0001 to 999,999, 0.0001 to 100,000, 0.001 to 1, 0.05 to 100, 10 to 300, 60 to 700, 50 to 75, 25 to 100, 2 to 10, 100 to 500, or 300 to 1000, 800 to 10,000 parts per million of a compound of Formula IV.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula VII in an amount of about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50%; and a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, and VUAA-1, a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI in an amount of about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50%, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, in the above method, the composition contains about 0.0001 to 999,999, 0.0001 to 100,000, 0.001 to 1, 0.05 to 100, 10 to 300, 60 to 700, 50 to 75, 25 to 100, 2 to 10, 100 to 500, or 300 to 1000, 800 to 10,000 parts per million of a compound of Formula VII.
In certain embodiments, the subject matter disclosed herein is directed to a method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula I′ in an amount of about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50%, and a compound of Formula II′ or a compound of Formula III′ in an amount of about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50%, wherein the composition is synergistic, in intimate admixture with a carrier.
In certain embodiments, in the above method, the composition contains about 0.0001 to 999,999, 0.0001 to 100,000, 0.001 to 1, 0.05 to 100, 10 to 300, 60 to 700, 50 to 75, 25 to 100, 2 to 10, 100 to 500, or 300 to 1000, 800 to 10,000 parts per million of a compound of Formula I′.
In certain embodiments, the subject matter described herein is directed to a method of repelling an arthropod from a locus to which said arthropod is normally attracted, comprising exposing said arthropod to any single compound described herein. In certain embodiments, the arthropod is exposed to said single compound in the form of a vapor active repellent. In certain embodiments, the benzaldehyde derivatives in Table 8 are repellents. In certain embodiments, the benzaldehyde derivatives in Table 8 are specifically vapor active repellents.
In certain embodiments, the arthropods repelled by the compounds, compositions, or methods disclosed herein are insects. In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Hemiptera Insects, selected from Delphacidae (planthoppers), such as Laodelphax striatellus (small brown planthopper), Nilaparvata hugens (brown planthopper), Sogatella furcifera (white-backed rice planthopper); Deltocephalidae (leafhoppers), such as Nephotettix cincticeps (green rice leafhopper), Recilia dorsalis (zig-zag rice leaf hopper), Nephotettix virescens (green rice leafhopper); Aphididae (aphids), stink bugs, Aleyrodidae (whiteflies), scales, Tingidae (lace bugs), or Psyllidae (suckers).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Lepidoptera Insects, selected from Pyralidae, such as Chilo suppressalis (rice stem borer), Cnaphalocrocis medinalis (rice leafroller), Plodia interpunctella (Indian meal moth); Noctuidae, such as Spodoptera litura (tobacco cutworm), Pseudaletia separata (rice armyworm), Mamestra brassicae (cabbage armyworm); Pieridae, such as Pieris rapae crucivora (common cabbageworm); Tortricidae, such as Adoxophyes spp.; Carposinidae; Lyonetiidae; Lymantriidae; Plusiinae; Agrotis spp. such as Agrotis segetum (turnip cutworm), or Agrotis ipsilon (black cutworm); Helicoverpa spp.; Heliothis spp.; Plutella xylostella; Parnara guttata (rice skipper); Tinea pellionella (casemaking clothes moth); or Tineola bisselliella (webbing clothes moth).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Diptera Insects, Culex spp., such as Culex pipiens pallens (common mosquito), Culex tritaeniorhynchus, Aedes spp., such as Aedes aegypti, Aedes albopictus; Anopheles spp., such as Anopheles sinensis; Chironomidae (midges); Muscidae, such as Musca domestica (housefly), Muscina stabulans (false stablefly), Fannia canicularis (little housefly); Calliphoridae; Sarcophagidae; Anthomyiidae, such as Delia platura (seedcorn maggot), Delia antiqua (onion maggot); Tephritidae (fruit flies); Drosophilidae; Psychodidae (moth flies); Tabanidae; Simuliidae (black flies); Stomoxyidae (stable flies); Phoridae; or Ceratopogonidae (biting midges).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Coleoptera Insects (Beetles), several nonlimiting examples of which include Corn rootworms, such as Diabrotica virgifera (western corn rootworm), Diabrotica undecimpunctata howardi (southern corn rootworm); Scarabaeidae (scarabs), such as Anomala cuprea (cupreous chafer), Anomala rufocuprea (soybean beetle); Curculionidae (weevils), such as Sitophilus zeamais (maize weevil), Lissorhoptrus oryzophilus (ricewater weevil), ball weevil, Callosobruchus chinensis (adzuki bean weevil); Dermestidae, such as Authrenus verbasci (varied carpet beetle), Attagenus unicolor japonicus (black carpet beetle); Tenebrionidae (darkling beetles), such as Tenebrio molitor (yellow mealworm), or Tribolium castaneum (red flour beetle); Chrysomelidae (leaf beetles) such as Oulema oryzae (rice leaf beetle), Phyllotreta striolata (striped flea beetle), Aulacophora femoralis (cucurbit leaf beetle); Anobiidae; Epilachna spp. such as Epilachna vigintioctopunctata (twenty-eight-spotted ladybird); Lyctidae (powderpost beetles), Bostrychidae (false powderpost beetles), or Cerambycidae, Paederus fuscipes (robe beetle).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Dictyoptera Insects, such as the following: Blattella germanica (German cockroach); Periplaneta filiginosa (smokybrown cockroach); Periplaneta americana (American cockroach); Periplaneta brunnea (brown cockroach); or Blatta orientalis (oriental cockroach).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Thysanoptera Insects (Thrips), such as Thrips palmi, Flankliniella occidentalis (western flower thrips), or Thrips hawaiiensis (flower thrips).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Hymenoptera Insects, such as Formicidae (ants); Vespidae (hornets); Polistes spp. (long-legged wasps); Bethylidae; or Tenthredinidae (sawflies), such as Athalis rosae ruficornis (cabbage sawfly).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Orthoptera Insects, such as Gryllotalpidae (mole crickets); or Acrididae (grasshoppers).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Siphonaptera Insects (Fleas), such as Ctenocephalides canis (dog flea); Ctenocephalides felis (cat flea); or Pulex irritans.
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Anoplura Insects (Lice), such as Pediculus corporis (body louse); Pediculus humanus (head louse); or Pthirus pubis (crab louse).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Isoptera Insects, such as Reticulitermes speratus; Coptotermes formosanus (Formosan subterranean termite).
In certain embodiments, the insects repelled by the compounds, compositions, or methods disclosed herein are Harmful Acarina, such as Ixodidae (Ticks): Boophilus microplus; Haemaphysalis longiconis Tetranychidae (spider mites): Tetranychus cinnabarimus (carmine spider mite); Tetranychus urticae (two-spotted spider mite); Tetranychus kanzawai (Kanzawa spider mite); Panonychus citri (citrus red mite); Panonychus ulmi (European red mite); House-dust Mites: Acaridae such as Tyrophagus putrescentiae (copra mite), Aleuroglyphus ovatus (brown legged grain mite); Dermanyssidae such as Dermatophagoides farinae (American house dust mite), Dermatophagoides pteronyssinus; mites parasitizing honeybees, such as Varroa jacobsoni; Euvarroa sinhai, Acarapis woodi; Tropilaelaps clareae; Glycyphagidae, such as Glycyphagus privatus, Glycyphagus domesticus, Glycyphagus destructor; Cheyletidae, such as Chelacaropsis malaccensis, Cheyletus fortis; Tarsonemidae; Chortoglyphus spp.; Haplochthonius spp. Chilognatha (millipedes), such as Oxydus spp.; Chilopoda (centipedes), such as red centipede; wood lice, such as Porcellio spp., Porcellionides spp.; and pill bugs, such as Armadillidium spp.
In certain embodiments, the arthropod repelled by the compounds, compositions, or methods disclosed herein is selected from the group consisting of a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, and scorpion. In certain embodiments, the arthropod repelled by the compounds, compositions, or methods disclosed herein is selected from the group consisting of a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, scorpion, roache, ant, termite, silverfish, and wasp. In certain embodiments, the arthropod is an insect.
In certain embodiments, the insect is a mosquito. In certain embodiments, the mosquito genera is selected from the group consisting of Culex, Anopheles, and Aedes. In certain embodiments, the mosquito is of the species, Aedes aegypti.
In certain embodiments, the subject matter described herein is directed to a method of controlling one or more insects, comprising contacting the insects with a synergistic composition comprising a compound of Formula II′ or a compound of Formula III′ in an amount of about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50% and a pyrethroid in an amount of about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50%, wherein the synergistic composition produces, when the insects are brought into contact with the synergistic composition, a combined toxicant effect greater than the sum of the separate toxicant effects from the compound of Formula II′ or Formula III′ and the pyrethroid, at comparable concentrations.
In certain embodiments, in the above method, the composition contains about 0.0001 to 999,999, 0.0001 to 100,000, 0.001 to 1, 0.05 to 100, 10 to 300, 60 to 700, 50 to 75, 25 to 100, 2 to 10, 100 to 500, or 300 to 1000, 800 to 10,000 parts per million of a compound of Formula II′ or Formula III′.
In certain embodiments, the subject matter described herein is directed to a method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising an essential oil in an amount of about 0.01-99.99%, 1-99%, 5-95%, 10-90%, 20-80%, 30-70%, 40-60%, or 50%, and a second compound in an amount of about 99.99-0.01%, 99-1%, 95-5%, 90-10%, 80-20%, 70-30%, 60-40%, or 50%, selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, and Formula VII, wherein the composition is synergistic, in intimate admixture with a carrier.
As used herein, “controlling one or more insects” or “controlling one or more arthropods” refers to mitigating or reducing a population of insects or a population of arthropods, respectively. In certain embodiments, the synergistic methods disclosed herein achieve a combined toxicant effect greater than 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% than the sum of the separate toxicant effects from the compound of Formula II′ or Formula III′ and the second compound, at comparable concentrations.
In certain embodiments, the toxicant effect refers to the vapor toxicity of the synergistic composition.
Flash column chromatography (CombiFlash Rf 200i) was performed using silica gel (RediSep Rf Gold Normal-Phase Silica) purchased from TELEDYNE ISCO. Thin layer chromatography (TLC) was performed on silica gel matrix on TLC Al foils with fluorescent indicator 254 nm, purchased from Sigma-Aldrich. All hexane used was a mixture of hexanes. Reagents were purchased from Sigma-Aldrich and were used without purification, unless otherwise noted.
Exemplary Methods for Preparing Compounds of Formula I
Method A. Briefly, thionyl chloride (1.4 equiv) was added dropwise to a solution of carboxylic acid (1 equiv) in methanol (5 mL/mmol). The mixture was vigorously stirred and monitored by TLC. Upon completion, the crude mixture was concentrated under reduced pressure with a rotoevaporator and purified on a silica gel column (Tetrahedron 69 (2013) 10946-10954).
Method B. Alcohol (1 equiv), carboxylic acid (1.2 equiv) and 4-dimethylaminopyridine (0.15) were dissolved in dichloromethane (1 mL/mmol) and cooled to 0° C. N,N-dicyclohexylcarbodiimide (1.05 equiv) in dichloromethane (2 mL/mmol) was added dropwise over 5 minutes, and the mixture was stirred for 0.25 hours at 0° C. The mixture was warmed to room temperature and stirred for 16 hours. The mixture was cooled at 0° C. for one hour and then filtered. The filtrate was washed with hexane, and the mother liquor was collected and concentrated in vacuo. The crude mixture was placed directly on and purified by silica gel column chromatography (Klimavicz et al. 2018).
Method C. Carboxylic acid (1 equiv) was added to a suspension of potassium carbonate (1.21 equiv) in acetone (1.6 mL/mmol) at room temperature and stirred for 0.5 hours. The mixture was cooled to 0° C., alkyl halide (1.53 equiv) was added, and the reaction was refluxed overnight for 16 hours. The mixture was cooled to room temperature and filtered through a celite plug. The mother liquor was concentrated under reduced pressure and purified by silica gel chromatography (G. Esteban et al. Tetrahedron 54 (1998) 197-212). Compositions comprising two or more compounds can be prepared by contacting the two or more compounds, optionally in the presence of a suitable carrier.
Exemplary Procedure for the Hydrolysis of Pyrethroids
Method D. Pyrethroid (1 equiv) was suspended in NaOH(aq) or KOH(aq) (1M, 5 equiv) and methanol (10 mL/mmol) and refluxed for 16 hours. The mixture was cooled to room temperature, concentrated by rotoevaporation, and extracted with ethyl acetate. The organic layer obtained through extraction from the basic aqueous layer was collected, dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by silica gel column chromatography to afford the hydrolyzed alcohol. The basic aqueous layer was then collected and acidified with 1M HCl. The now acidic aqueous layer was then extracted with ethyl acetate. The organic layer obtained through extraction from the acidic aqueous layer was collected, dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by silica gel column chromatography to afford the hydrolyzed carboxylic acid.
Method E. KOH (10 equiv) was added to a solution of pyrethroid (1 equiv) in MeOH/H2O (5 mL/mmol) and stirred for 16 hours at room temperature. The mixture was concentrated by rotoevaporation, and extracted with ethyl acetate. The organic layer obtained through extraction from the basic aqueous layer was collected, dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by silica gel column chromatography to afford the hydrolyzed alcohol. The basic aqueous layer was then collected and acidified with 1M HCl. The now acidic aqueous layer was then extracted with ethyl acetate. The organic layer obtained through extraction from the acidic aqueous layer was collected, dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by silica gel column chromatography to afford the hydrolyzed carboxylic acid.
Exemplary Procedure for Conversion of Cyanohydrin to Aldehyde and Carboxylic Acid
Method F. KOH (5 equiv) was added to a solution of cyanohydrin (1 equiv) in 1/1 Dioxane/H2O (10 mL/mmol), and the solution was stirred for 16 hours. The mixture was extracted with ethyl acetate. The organic layer obtained through extraction from the basic aqueous layer was collected, dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by silica gel column chromatography to afford the aldehyde. The basic aqueous layer was then collected and acidified with 1M HCl(aq). The now acidic aqueous layer was then extracted with ethyl acetate. The organic layer obtained through extraction from the acidic aqueous layer was collected, dried with magnesium sulfate, filtered, concentrated in vacuo, and purified by silica gel column chromatography to afford the hydrolyzed carboxylic acid.
Compounds can be synthesized by synthetic routes that include processes analogous to those well-known in the chemical arts, particularly in light of the description contained herein, and those for other heterocycles described in: Comprehensive Heterocyclic Chemistry II, Editors Katritzky and Rees, Elsevier, 1997, e.g., Volume 3; Liebigs Annalen der Chemie, (9):1910-16, (1985); Helvetica Chimica Acta, 41:1052-60, (1958); Arzneimittel-Forschung, 40(12):1328-31, (1990), each of which are expressly incorporated by reference. Starting materials are generally available from commercial sources such as Aldrich Chemicals (Milwaukee, Wis.) or are readily prepared using methods well known to those skilled in the art (e.g., prepared by methods generally described in Louis F. Fieser and Mary Fieser, Reagents for Organic Synthesis, v. 1-23, Wiley, N.Y. (1967-2006 ed.), or Beilsteins Handbuch der organischen Chemie, 4, Aufl. ed. Springer-Verlag, Berlin, including supplements (also available via the Beilstein online database). DTT refers to dithiothreitol. DHAA refers to dehydroascorbic acid.
Synthetic chemistry transformations and protecting group methodologies (protection and deprotection) useful in synthesizing compounds and necessary reagents and intermediates are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley and Sons (1999); and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995) and subsequent editions thereof.
Compounds may be prepared singly or as compound libraries comprising at least 2, for example 5 to 1,000 compounds, or 10 to 100 compounds. Libraries of compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula I′, Formula II′, or Formula III′ may be prepared by a combinatorial ‘split and mix’ approach or by multiple parallel syntheses using either solution phase or solid phase chemistry, by procedures known to those skilled in the art. Thus, according to a further aspect, there is provided a compound library comprising at least 2 compounds, or agrochemically acceptable salts thereof.
Compositions comprising two or more compounds can be prepared simply by contacting one with the other.
The General Procedures and Examples provide exemplary methods for preparing compounds. Those skilled in the art will appreciate that other synthetic routes may be used to synthesize the compounds. Although specific starting materials and reagents are depicted and discussed in the Schemes, General Procedures, and Examples, other starting materials and reagents can be easily substituted to provide a variety of derivatives and/or reaction conditions. In addition, many of the exemplary compounds prepared by the described methods can be further modified in light of this disclosure using conventional chemistry well known to those skilled in the art.
In another aspect, described herein are articles of manufacture, for example, a “kit,” containing materials useful for repelling one or more insects. According to one embodiment, a kit may comprise (a) a first container with a compound of Formula II contained therein, such as transfluthrin acid; and (b) a second container comprising a second compound, such as DEET, contained therein.
The kit may further comprise a label or package insert, on or associated with the containers. The term “package insert” is used to refer to instructions customarily included in commercial packages of insect repellent products, that contain information about the usage, applications, and/or warnings concerning the use of such insect repellent products. The kit may include an applicator for spreading the compounds onto a surface. The label or package insert indicates that the composition is used for repelling the insect of choice, such as mosquitos.
The kit may further comprise directions for the application of the compound of Formula II and the second compound. For example, the kit may further comprise directions for the simultaneous, sequential or separate application of the first and second compounds.
In certain other embodiments, wherein the kit comprises a composition of Formula II and a second compound, such as DEET, the kit may comprise a container for containing the separate compositions such as a divided bottle or a divided foil packet, however, the separate compositions may also be contained within a single, undivided container. Typically, the kit comprises directions for the application of the separate components. The kit form is particularly advantageous when the separate components are preferably applied in separate steps (e.g., not in mixed compositions), but separately on a surface, side-by-side.
As used herein, non-limiting examples of pyrethroids include permethrins, tetramethrin, metoflurthrin, bifenthrin, kappa-bifenthrin, kadethrin, allethrin, bioallethrin, cyfluthrin, beta-cyfluthrin, deltamethrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, kappa-tefluthrin, phenothrin, etofenprox, fluvalinate, acrinathrin, halfenprox, flubrocythrinate, bioethanomethrin, brofenvalerate, brofluthrinate, bromethrin, butethrin, chlorempenthrin, cylethrin, cycloprothrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, dimethfluthrin, dimethrin, empenthrin, chloroprallethrin, fenfluthrin, fenpirithrin, fenpropathrin, flucythrinate, fluvalinate, tau-fluvalinate, furamethrin, furethrin, heptafluthrin, imiprothrin, japothrins, methothrin, metofluthrin, epsilon-metofluthrin, momfluorothrin, epsilon-momfluorothrin, pentmethrin, biopermethrin, transpermethrin, profluthrin, proparthrin, pyresmethrin, renofluthrin, meperfluthrin, resmethrin, bioresmethrin, cismethrin, terallethrin, tetramethylfluthrin, tralocythrin, tralomethrin, valerate, flufenprox, halfenprox, protrifenbute, silafluofen, sulfoxime, thiofluoximate, and transfluthrin.
As used herein, non-limiting examples of essential oils include Almond Oil Bitter, Almond Oil Sweet, Amyris Oil W.I., Angelica Root Oil, Angelica Seed Oil, Anise Oil Chinese, Anise Oil Spanish, Anise Oil Vietnam, Aniseed Oil, Aniseed Oil Terpenes, Apricot Kernel Oil, Armoise Oil, Artemesia Afra, Asafoetida Oil, Avocado Oil, Balsam Copaiba, Balsam Copaiba Oil, Balsam Fir Canada, Balsam Peru, Balsam Peru Oil, Balsam Tolu PG, Basil Oil Comores Type, Basil Oil Indian, Basil Oil Linalool Type, Bay Oil Terpeneless Type, Bay Oil W.I., Bay Oil W.I. Bleached & Filtered, Bay Terpenes PG, Beeswax Absolute, Benzoin Siam Resin, Bergamot Oil, Bergamot Oil B.F., Bergamot Oil Residues, Bergamot Oil Terpenes, Birch Tar Crude, Birch Tar Rectified, Black Currant Bud Absolute, Blood Orange Oil, Bois de Rose Oil, Boronia Absolute Tasmanian, Brominated Vegetable Oil, Buchu Leaf Oil Betulina, Buchu Leaf Oil Crenulata, Buchu Oil, Sulfur Fractions 40%, Cabreuva Oil, Cade Oil, Cade Oil Rectified, Cajeput Oil, Calamus Oil, Camphor Oil 1.070, Camphor Oil Chinese, Camphor Oil White Taiwan, Cananga Oil, Caraway Oil, Cardamom Oil, Carrot Seed Oil, Carvene, Cascarilla Bark Oil, Cassia Oil, Catnip Oil, Cedarleaf Oil, Cedarwood Oil (i.e. Cedarwood Oil Atlas, Cedarwood Oil Chinese, Cedarwood Oil Texas, Cedarwood Oil Texas Redistilled, and Cedarwood Oil Virginiana), Celery Seed Oil, Chamomile Oil Blue, Chamomile Oil Roman, Chamomile Oil Wild Maroc, Cinnamon Bark Oil, Cinnamon Leaf Oil Ceylon, Cistus Absolute, Cistus Oil, Citronella Oil Java 85/35, Citronella Oil Chinese 85/35, Citronella Oil Ceylon, Citronella Terpenes, Clove Bud Indonesian, Clove Bud Oil Prime, Clove Leaf Oil Indonesian 70/80, Clove Leaf Oil Madagascar 80/82, Clove Leaf Oil Redistilled, Clove Stem Oil, Clove Terpenes, Coffee Oil, Cognac Oil Green, Cognac Oil White, Coriander Herb Oil (Cilantro), Coriander Seed Oil, Cornmint Oil 50% Dementh. India, Cornmint Oil 50% Dementh. China, Cornmint Oil Rectified, Cubeb Oil, Cumin Seed Oil, Cypress Oil, Davana Oil, Dillseed Oil, Dillweed Oil, Eucalyptus Citriodora Brazil, Eucalyptus Citriodora Chinese, Eucalyptus Oil 70/75, Eucalyptus Oil 80/85, Eucalyptus Oil Terpenes, Eucalyptus Smithii Oil S.A., Evening Primrose, Fennel Oil, Fennel Oil Bitter, Fennel Oil Sweet, Fir Balsam Absolute, Fir Balsam Concrete, Fir Balsam Canadian, Fir Needle Oil Canadian, Fir Needle Oil Siberian, Fir Needle Oil Chinese, Galangal Root Oil, Galbanum Oil, Galbanum Resinoid, Garlic Oil Chinese, Garlic Oil Mexican, Genet Absolute, Geranium Oil Chinese, Geranium Oil Egyptian, Ginger Oil Chinese, Ginger Oil Fresh, Ginger Oil Indian, Grapefruit Oil 5×, Grapefruit Oil Pink C.P., Grapefruit Oil Washed, Grapefruit Oil White C.P., Grapefruit Terpenes, Grapeseed Oil, Gum Benzoin Siam Resin, Gurjon Balsam Oil, Guaiacwood Oil, Helichrysum Oil, Hemlock Oil, Ho Leaf Oil, Hop Oil, Horseradish Oil, Howood Oil 95%, Hyssop Oil, Jasmine Absolute, Jojoba Oil Purified White, Juniperberry Oil, Labdanum Gum Refined, Lanyana Oil, Laurel Leaf Oil, Lavandin Abrialis, Lavandin Grosso, Lavender Absolute Bulgarian, Lavender Oil 16%, Lavender Oil 40/42 French, Lavender Oil Bulgarian, Lavender Oil Spike, Lemon Essence Oil, Lemon Oil Argentina, Lemon Oil Brazil, Lemon Oil California 5×, Lemon Oil California Type, Lemon Oil Distilled, Lemon Oil Israeli, Lemon Oil Washed, Lemon Terpenes, Lemongrass Oil Guatemalan, Lemongrass Oil East Indian, Lemongrass Terpenes, Lemongrass Oil Terpeneless, Lime Essence Oil Phase, Lime Oil Mexican C.P., Types A & B, Lime Oil Distilled Mexican, Lime Oil Distilled Terpenes, Lime Oil Expressed Terpenes, Lime Oil Peru Distilled, Lime Oil Washed, Lime Sesqui Fractions, Lime Terpenes, Litsea Cubeba Oil, Litsea Terpenes, Lovage Leaf Oil, Lovage Root Oil, Mandarin Essence Oil Phase, Mandarin Oil Brazil, Mandarin Oil Green, Mandarin Oil Italian, Mandarin Oil Red Argentina, Mandarin Terpenes, Mandarin Petitgrain Terpeneless, Marjoram Oil Spanish, Marjoram Oil Sweet Egyptian, Massoia Bark Oil, Melissa Oil, Mentha Arvensis Oil, Mentha Citrata Oil, Mentha Piperita Oil, Milfoil Oil, Mimosa Absolute, Mousse de Arbre, Mousse de Pin Absolute, Mustard Oil Natural, Mustard Oil Synthetic, Myrrh Oil, Myrtle Oil, Neroli Oil, Nutmeg Oil, Nutmeg Oil Ceylon, Nutmeg Oil E.I., Nutmeg Terpenes, Oakmoss Absolute Green, Ocotea Cymbarum, Olibanum Oil, Olibanum Resin, Opoponax Oil, Onion Oil Egyptian, Onion Oil Mexican, Orange Juice Oil BJ N&A, Orange Essence Oil Phase, Orange Oil 5×, Orange Oil 10×, Orange Oil Bitter Ivory Coast Type, Orange Oil Bitter West Indian, Orange Oil Bitter Brazil, Orange Oil S.A., Orange Oil Midseason, Orange Oil Valencia, Orange Oil Terpeneless, Orange Terpenes, Organic Artemesia Oil, Organic Balsam Copaiba Oil, Organic Bois de Rose Oil, Organic Dillweed Oil, Organic Juniper Berry Oil, Organic Lavender Oil, Bulgarian, Organic Peppermint Oil, Organic Tea Tree Oil, Organic Wormwood Oil European, Organic Zdravetz Oil, Origanum Oil, Orris Root Concrete 8% Irone, Palmarosa Oil, Parsley Leaf Oil, Parsley Seed Oil, Patchouli Oil Indonesian, Patchouli Oil Light, Patchouli Oil Molecular Distilled, Pennyroyal Oil, Pepper Oil Black, Peppermint Oil Hotchkiss Type, Peppermint Oil Mitcham Type, Peppermint Oil Piperita Chinese, Peppermint Oil Piperita Indian, Peppermint Oil Piperita Redistilled, Peppermint Oil Piperita Williamette, Peppermint Oil Piperita Yakima, Peppermint Oil Terpenes, Perilla Oil, Petitgrain Oil S.A., Petitgrain Terpenes, Pimento Berry Oil, Pimento Leaf Oil, Pink Pepper Oil (Schinus Molle), Pinus Oil Pumilio, Pinus Oil Sylvestris, Rose Absolute Bulgarian, Rose Absolute Maroc, Rose Concrete Bulgarian, Rose Oil Bulgarian, Rose Oil Maroc, Rose Oil Turkish, Rose Water Concentrate, Rosemary Oil Maroc, Rosemary Oil Spanish, Rosemary Oil Tunisian, Rue Oil, Sage Oil 30%, Sage Oil 50%, Sage Oil Clary, Sage Oil Spanish, Sandalwood Oil Australian, Sandalwood Oil East Indian, Sandalwood Oil Indonesian, Sandalwood Oil Sri Lanka, Sassafras Oil, Savory Oil, Siamwood Oil, Spearmint Oil 65% Indian, Spearmint Oil Chinese 60%, Spearmint Oil Chinese 80%, Spearmint Oil Native, Spearmint Oil Terpeneless, Spearmint Terpenes, Spike Lavender Oil, Spikenard Oil, Spruce Absolute, Spruce Oil Canadian, Styrax Gum Honduras, Styrax Oil Honduras, Tagetes Oil Argentina, Tagetes Oil South African, Tagetes Oil Zimbabwe, Tangerine Oil 5×, Tangerine Oil 10×, Tangerine Oil CP China, Tangerine Oil CP Cravo, Tangerine Oil CP Florida, Tangerine Terpenes, Tarragon Oil, Tea Tree Oil, Thuja Oil, Thyme Oil Red, Thyme Oil White, Tolu Balsam, Tonka Bean Absolute, Perfume Grade, Treemoss Absolute, Tuberose Absolute, Valerian Root Oil, Vetiver Oil Indonesian, Vetiver Terpenes, Vetiver Oil Brazil, Violet Leaf Absolute, Wintergreen Oil Redistilled, Wormwood Oil American, Wormwood Oil European, Yarrow Oil (Milfoil), Ylang Oil #1, Ylang Oil #2, Ylang Oil #3, Ylang Oil Extra, and Zdravetz Oil.
As described herein, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, nootkatone, and VUAA-1 are chemical compounds with repellent properties.
The IUPAC name for methyl jasmonate is Methyl (1R,2R)-3-Oxo-2-(2Z)-2-pentenyl-cyclopentaneacetate. Methyl jasmonate is a volatile organic compound often used in plant defense and many diverse developmental pathways, such as seed germination, root growth, flowering, fruit ripening, and senescense (Cheong, Jong-Joo; Choi, Yang Do (July 2003). “Methyl jasmonate as a vital substance in plants”. Trends in Genetics. 19(7): 409-413.)
IR3535 is the trade name for ethyl butylacetylaminopropionate. IR3535 is an insect repellent.
2-undecanone is also known as methyl nonyl ketone or IBI-246. It a colorless oil typically used as an insect repellent.
Picaridin is also known as Icaridin. It IUPAC name is 1-(1-Methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine. Picaridin is a near colorless and odorless insect repellent.
p-menthane-3,8-diol is also known aspara-menthane-3,8-diol, PMD, or menthoglycol. Its IUPAC name is 2-(2-Hydroxypropan-2-yl)-5-methylcyclohexan-1-ol.
The IUPAC name for alpha-terpineyl isovalerate is 2-(4-methylcyclohex-3-en-1-yl)propan-2-yl 3-methylbutanoate.
The IUPAC name for VUAA1 is 2-(4-Ethyl-5-(pyridin-3-yl)-4H-1,2,4-triazol-3-ylthio)-N-(4-ethylphenyl)acetamide. VUAA1 is a chemical compound that works by over activating an insect's olfactory senses, causing a repellent effect (Jones, P. L., Pask, G. M., Rinker, D. C., & Zwiebel, L. J. (2011). PNAS, 108(21), 8821-8825.).
The subject matter described herein includes the following embodiments:
1. A compound of Formula I
wherein R1 and R2 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R1 and R2 are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R3 and R4 are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R5 is selected from the group consisting of linear or branched C5-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C5 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl; and
X is selected from the group consisting of O, NH, and S.
2. The compound of embodiment 1, wherein R3 and R4 are each C1-C3 alkyl.
3. The compound of embodiment 1 or 2, wherein R3 and R4 are each methyl.
4. The compound of any one of embodiments 1-3, wherein R1 and R2 are each halo.
5. The compound of any one of embodiments 1-4, wherein R1 and R2 are each independently selected from chloro, bromo, iodo, and fluoro.
6. The compound of any one of embodiments 1-5, wherein R1 and R2 are each independently chloro.
7. The compound of any one of embodiments 1-6, wherein X is O.
8. The compound of any one of embodiments 1-7, wherein X in NH.
9. The compound of any one of embodiments 1-8, wherein R5 is selected from the group consisting of linear C5-C12 alkyl, haloalkyl, and C3-C5 cycloalkyl.
10. The compound of any one of embodiments 1-9, wherein R5 is selected from the group consisting of pentyl, trifluoroethyl, cyclobutyl, cyclopentyl, and cyclopropyl.
11. The compound of any one of embodiments 1-10, wherein said compound is selected from the group consisting of:
12. A composition comprising a compound of any one of embodiments 1-11 and a carrier.
13. A composition comprising about 0.01-99.99% of a compound of Formula II′ or a compound of Formula III′:
where R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl, and
about 99.99-0.01% of a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1,
wherein the composition is synergistic, in intimate admixture with a carrier.
14. The composition of embodiment 13, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, and tea tree oil.
15. The composition of embodiment 13 or 14, wherein said essential oil is citronella oil.
16. The composition of any one of embodiments 13-15, wherein said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
17. The composition of any one of embodiments 13-16, wherein said composition comprises a compound of Formula II′, wherein X″ is O.
18. The composition of any one of embodiments 13-17, wherein R8′ and R9′ are each methyl.
19. The composition of any one of embodiments 13-18, wherein said compound of Formula II′ is
20. The composition of any one of embodiments 13-19, comprising about 0.01-99.99% of
and about 99.99-0.01% transfluthrin.
21. The composition of any one of embodiments 13-20, comprising about 0.01-99.99%
and about 99.99-0.01% citronella oil.
22. The composition of any one of embodiments 13-21, wherein said composition comprises about 0.01-99.99%% of a compound of Formula II′ and about 99.99-0.01% citronella oil.
23. A composition comprising about 0.01-99.99% of a compound of Formula IV, a compound of Formula V, or a compound of Formula VI:
wherein Y is selected from the group consisting of O, NH, and S;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, and linear or branched C1-C6 alkyl; and
about 0.01-99.99% of a compound of Formula II′ or a compound of Formula III′:
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in intimate admixture with a carrier.
24. The composition of embodiment 23, wherein said composition comprises about 20-80% of a compound of Formula IV, a compound of Formula V, or a compound of Formula VI, and about 80-20% of a compound of Formula II′ or a compound of Formula III′.
25. The composition of embodiment 23 or 24, wherein said composition comprises about 40-60% of a compound of Formula IV, a compound of Formula V, or a compound of Formula VI, and about 60-40% of a compound of Formula II′ or a compound of Formula III′.
26. The composition of any one of embodiments 23-25, wherein said composition comprises about 0.01-99.99% a compound of Formula VI and about 99.99-0.01% a compound of Formula II′.
27. The composition of any one of embodiments 23-26, wherein said compound of Formula VI is
and said compound of Formula II′ is
28. A composition comprising about 0.01-99.99% of a compound of Formula VII
wherein R28 is selected from the group consisting of hydrogen, haloalkyl, alkoxy, alkenyl, alkynyl, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, alkoxy, halo, cyano, haloalkyl, alkenyl, alkynyl, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy; and
about 99.99-0.01% of a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, VUAA-1, a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
Y is selected from the group consisting of O, NH, and S;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, alkenyl, alkynyl, haloalkyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in intimate admixture with a carrier.
29. The composition of embodiment 28, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, and tea tree oil.
30. The composition of embodiment 28 or 29, wherein said essential oil is citronella oil.
31. The composition of any one of embodiments 28-30, wherein said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
32. The composition of any one of embodiments 28-31, wherein said composition comprises about 0.01-99.99% of a compound of Formula VII and about 99.99-0.01% of a compound selected from citronella oil and a compound of Formula II′.
33. The composition of any one of embodiments 28-32, wherein said composition comprises about 0.01-99.99% of a compound of Formula VII and about 99.99-0.01% of a compound selected from the group consisting of a compound of Formula IV, V, and VI.
34. The composition of any one of embodiments 28-33, wherein R30, R31, R32, and R34 are each hydrogen.
35. The composition of any one of embodiments 28-34, wherein R33 is
36. The compound of any one of embodiments 28-35, wherein R40, R41, R42, R43, and R44 are each hydrogen.
37. The composition of any one of embodiments 28-36, wherein M is O.
38. The composition of any one of embodiments 28-37, wherein R29 is hydrogen.
39. The composition of any one of embodiments 28-38, wherein said compound of Formula VII is
40. The composition of any one of embodiments 28-39, wherein said composition comprises from 0.01-99.99% of a compound of Formula VII having the structure
and from 99.99 to 0.01% of a compound of Formula II′ having the structure
41. The composition of any one of embodiments 28-40, wherein said composition comprises from 0.01-99.99% of a compound of Formula VII having the structure
and from 99.99 to 0.01% of a compound of Formula II′ having the structure
42. The composition of any one of embodiments 28-41, wherein said composition comprises from 0.01-99.99% of a compound of Formula VII having the structure
and from 99.99-0.1% of citronella oil.
43. The composition of any one of embodiments 28-42, wherein said composition comprises from 0.01-99.99% of a compound of Formula VII having the structure
and from 99.99-0.01% of a compound of Formula VI having the structure
44. A composition comprising about 0.01-99.99% of a compound of Formula I′ and about 99.99-0.01% of a compound of Formula II′ or a compound of Formula III′
wherein R1′ and R2′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R1′ and R2′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R3′ and R4′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R5′ is selected from the group consisting of linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X′ is selected from the group consisting of O, NH, and S;
R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R1′ and R2′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl, and
wherein the composition is synergistic, in intimate admixture with a carrier.
45. The composition of embodiment 44, wherein said composition comprises from 0.01-99.99% of a compound of Formula I′ and from 99.99 to 0.01% of a compound of Formula II′, wherein said compound of Formula II′ is
46. The composition of embodiment 44 or 45, wherein R3′ and R4′ are each methyl.
47. The composition of any one of embodiments 44-46, wherein X′ is O.
48. The composition of any one of embodiments 44-47, wherein R5′ is linear or branched C1-C6 alkyl.
49. The composition of any one of embodiments 44-48, wherein R5′ is C3-C6 cycloalkyl.
50. A method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula II′ or a compound of Formula III′ in an amount of about 0.01-99.99%:
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1, in an amount of about 99.99-0.01%,
wherein the composition is synergistic, in intimate admixture with a carrier.
51. The method of embodiment 50, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, and tea tree oil.
52. The method of embodiment 50 or 51, wherein said essential oil is citronella oil.
53. The method of any one of embodiments 50-52, wherein said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
54. The method of any one of embodiments 50-53, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′ or a compound of Formula III′.
55. The method of any one of embodiments 50-54, wherein the composition is a solution, dust, granular formulation or emulsion.
56. The method of any one of embodiments 50-55, wherein the composition is a liquid solution or emulsion.
57. The method of any one of embodiments 50-56, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′ or a compound of Formula III′.
58. The method of any one of embodiments 50-57, wherein said species of insect is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
59. The method of any one of embodiments 50-58, wherein said insect is a mosquito.
60. The method of any one of embodiments 50-59, where the locus is an area, an environment, or the skin of an animal.
61. The method of any one of embodiments 50-60, wherein said composition comprises a compound of Formula II′.
62. The method of any one of embodiments 50-61, wherein X″ is O.
63. The method of any one of embodiments 50-62, wherein R8′ and R9′ are each C1-C6 alkyl.
64. The method of any one of embodiments 50-63, wherein R8′ and R9′ are each methyl.
65. The method of any one of embodiments 50-64, wherein R7′ and R6′ are each independently selected from halogen or C1-C6 alkyl.
66. The method of any one of embodiments 50-65, wherein said compound of Formula II′ is selected from
67. The method of any one of embodiments 50-66, wherein said composition comprises
and transfluthrin.
68. The method of any one of embodiments 50-67, wherein said composition comprises
and citronella oil.
69. A method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula IV, a compound of Formula V, or a compound of Formula VI in an amount of about 0.01-99.99%:
wherein Y is selected from the group consisting of O, NH, and S;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
a compound of Formula II′ or a compound of Formula III′ in an amount of about 99.99-0.01%:
R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in intimate admixture with a carrier.
70. The method of embodiment 69 wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula VI.
71. The method of embodiment 69 or 70, wherein R18 is hydrogen.
72. The method of any one of embodiments 69-71, wherein R13, R14, R16, and R17 are each halo.
73. The method of any one of embodiments 69-72, wherein R13, R14, R16, and R17 are each fluoro.
74. The method of any one of embodiments 69-73, wherein R16 is selected from hydrogen or C1-C3 alkyl-alkoxy.
75. The method of any one of embodiments 69-74, wherein said compound of Formula VI is
76. The method of any one of embodiments 69-75, wherein said composition comprises a compound of Formula VI and a compound of Formula II′.
77. The method of any one of embodiments 69-76, wherein X″ is O.
78. The method of any one of embodiments 69-77, wherein R8′ and R9′ are each methyl.
79. The method of any one of embodiments 69-78, wherein R7′ and R6′ are each independently selected from halogen or C1-C6 alkyl.
80. The method of any one of embodiments 69-79, wherein said compound of Formula VI is
81. The method of any one of embodiments 69-80, wherein said composition comprises a compound of Formula VI of
and a compound of Formula II′ of
82. The method of any one of embodiments 69-81, wherein the composition is a solution, dust, granular formulation or emulsion.
83. The method of any one of embodiments 69-82, wherein the composition is a liquid solution or emulsion.
84. The method of any one of embodiments 69-83, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula IV, Formula V, or Formula VI.
85. The method of any one of embodiments 69-84, wherein said species of insect is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
86. The method of any one of embodiments 69-85, wherein said insect is a mosquito.
87. The method of any one of embodiments 69-86, where the locus is an area, an environment, or the skin of an animal.
88. A method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula VII in an amount of about 0.01-99.99%
wherein R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, linear or branched C1-C6 alkyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy; and
a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, VUAA-1, a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI in an amount of about 99.99-0.01%
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
Y is selected from the group consisting of O, NH, and S;
R11 is selected from the group consisting of hydrogen, alkenyl, alkynyl, C1-C6 alkyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkylalkyl, arylalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, haloalkyl, alkenyl, alkynyl, halo, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in intimate admixture with a carrier.
89. The method of embodiment 88 wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula VII.
90. The method of embodiment 88 or 89, wherein R30, R31, R32, and R34 are each hydrogen.
91. The method of any one of embodiments 88-90, wherein R33 is
92. The method of any one of embodiments 88-91, wherein R40, R41, R42, R43, and R44 are each hydrogen.
93. The method of any one of embodiments 88-92, wherein M is O.
94. The method of any one of embodiments 88-93, wherein R28 is hydrogen.
95. The method of any one of embodiments 88-94, wherein said compound of Formula VII is
96. The method of any one of embodiments 88-95, wherein said composition comprises
and citronella oil.
97. The method of any one of embodiments 88-96, wherein said composition comprises
and a compound of Formula VI.
98. The method of any one of embodiments 88-97, wherein said composition comprises
99. The method of any one of embodiments 88-98, wherein said composition comprises
and a compound of Formula II′.
100. The method of any one of embodiments 88-99, wherein said composition comprises
101. The method of any one of embodiments 88-100, wherein said composition comprises
102. The method of any one of embodiments 88-101, wherein the composition is a solution, dust, granular formulation or emulsion.
103. The method of any one of embodiments 88-102, wherein the composition is a liquid solution or emulsion.
104. The method of any one of embodiments 88-103, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula VII.
105. The method of any one of embodiments 88-104, wherein said species of insect is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
106. The method of any one of embodiments 88-105, wherein said insect is a mosquito.
107. The method of any one of embodiments 88-106, where the locus is an area, an environment, or the skin of an animal.
108. A method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula I′ in an amount of about 0.01-99.99%
I′ and a compound of Formula II′ or a compound of Formula III′ in an amount of about 99.99-0.01%
wherein R1′ and R2′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R3′ and R4′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R5′ is selected from the group consisting of linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X′ is selected from the group consisting of O, NH, and S;
R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in intimate admixture with a carrier.
109. The method of embodiment 108, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula I′.
110. The method of embodiment 108 or 109, wherein R3′ and R4′ are each methyl.
111. The method of any one of embodiments 108-110, wherein X′ is O.
112. The method of any one of embodiments 108-111, wherein R5′ is linear or branched C1-C6 alkyl.
113. The method of any one of embodiments 108-112, wherein the composition is a solution, dust, granular formulation, or emulsion.
114. The method of any one of embodiments 108-113, wherein the composition is a liquid solution or emulsion.
115. The method of any one of embodiments 108-114, wherein the composition contains about 0.0001 to 100000 parts per million of the compound of Formula I′.
116. The method of any one of embodiments 108-115, wherein the composition contains a compound of Formula I′ and a compound of Formula II′.
117. The method of any one of embodiments 108-116, wherein X″ is O.
118. The method of any one of embodiments 108-117, wherein R6′ and R7′ are each independently selected from halo or C1-C6 alkyl.
119. The method of any one of embodiments 108-118, wherein R8′ and R9′ are each methyl.
120. The method of any one of embodiments 108-119, wherein the compound of Formula II″ is
121. The method of any one of embodiments 108-120, wherein the composition comprises a compound of Formula I′ and
122. The method of any one of embodiments 108-121, wherein the compound of Formula I′ is
123. The method of any one of embodiments 108-122, wherein said species of insect is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
124. The method of any one of embodiments 108-123, wherein said insect is a mosquito.
125. The method of any one of embodiments 108-124, where the locus is an area, an environment, or the skin of an animal.
126. A method for controlling one or more insects, comprising contacting the insects with a synergistic composition comprising a compound of Formula II′ or a compound of Formula III′ in an amount of about 0.01-99.99%:
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
a pyrethroid in an amount of about 99.99 to 0.01%,
wherein the synergistic composition produces, when the insects are brought into contact with the synergistic composition, a combined toxicant effect greater than the sum of the separate toxicant effects from the compound of Formula II′ or Formula III′ and the pyrethroid, at comparable concentrations.
127. The method of embodiment 126, wherein said toxicant effect is the vapor toxicity of the synergistic composition.
128. The method of embodiment 126 or 127, wherein the synergistic composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′ or Formula III′.
129. The method of any one of embodiments 126-128, wherein said synergistic composition comprises a compound of Formula II′ and transfluthrin.
130. The method of any one of embodiments 126-129, wherein X″ is O.
131. The method of any one of embodiments 126-130, wherein R6′ and R7′ are selected from halo or C1-C6 alkyl.
132. The method of any one of embodiments 126-131, wherein R8′ and R9′ are each independently C1-C3 alkyl.
133. The method of any one of embodiments 126-132, wherein R8′ and R9′ are each methyl.
134. The method of any one of embodiments 126-133, wherein said compound of Formula II is
135. The method of any one of embodiments 126-134, wherein said composition comprises
and transfluthrin.
136. The method of any one of embodiments 126-135, wherein the synergistic composition is a solution, dust, granular formulation or emulsion.
137. The method of any one of embodiments 126-136, wherein the synergistic composition is a liquid solution or emulsion.
138. The method of any one of embodiments 126-137, wherein the synergistic composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′.
139. The method of any one of embodiments 126-138, wherein said insects are flies, spiders, butterflies, crabs, mosquitos, centipedes, ticks, millipedes, or scorpions.
140. The method of any one of embodiments 126-139, wherein said insects are mosquitos.
141. A method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent composition comprising a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, or Formula VII
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S; and
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy.
142. The method of embodiment 141, wherein the composition is a solution, dust, granular formulation or emulsion.
143. The method of embodiment 141 or 142, wherein the composition is a liquid solution or emulsion.
144. The method of any one of embodiments 141-143, wherein said species of insect is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
145. The method of any one of embodiments 141-144, wherein said insect is a mosquito.
146. The method of any one of embodiments 141-145, wherein the mosquito is Aedes aegypti.
147. The method of any one of embodiments 141-146, where the locus is an area, an environment, or the skin of an animal.
148. The method of any one of embodiments 141-147, wherein said compound is of Formula II, wherein X is O and R10 is hydrogen.
149. The method of any one of embodiments 141-148, wherein R8 and R9 are each methyl.
150. The method of any one of embodiments 141-149, wherein said compound is selected from the group consisting of
151. The method of any one of embodiments 141-150, wherein said compound is of Formula III.
152. The method of any one of embodiments 141-151, wherein P is O and R27 is H.
153. The method of any one of embodiments 141-152, wherein R23 is halo and R21, R22, R24, and R25 are each hydrogen.
154. The method of any one of embodiments 141-153, wherein R23 is chloro.
155. The method of any one of embodiments 141-154, wherein said compound is
156. The method of any one of embodiments 141-155, wherein said compound is of Formula VI.
157. The method of any one of embodiments 141-156, wherein R13, R14, R16, and R17 are each halo.
158. The method of any one of embodiments 141-157, wherein R13, R14, R16, and R17 are each fluoro.
159. The method of any one of embodiments 141-158, wherein R15 is hydrogen.
160. The method of any one of embodiments 141-159, wherein R18 is hydrogen.
161. The method of any one of embodiments 141-160, wherein the compound of Formula VI is
162. The method of any one of embodiments 141-161, wherein the compound is of Formula IV.
163. The method of any one of embodiments 141-162, wherein Y is O.
164. The method of any one of embodiments 141-163, wherein R11 is CN.
165. The method of any one of embodiments 141-164, wherein the compound of Formula IV is
166. The method of any one of embodiments 141-165, wherein the compound is of Formula VII.
167. The method of any one of embodiments 141-166, wherein R30, R31, R32, and R34 are each hydrogen.
168. The method of any one of embodiments 141-167, wherein R33 is
169. The method of any one of embodiments 141-168, wherein R40, R41, R42, R43, and R44 are each hydrogen.
170. The method of any one of embodiments 141-169, wherein M is O.
171. The method of any one of embodiments 141-170, wherein R28 is H.
172. The method of any one of embodiments 141-171, wherein the compound of Formula VII is
173. The method of any one of embodiments 141-172, wherein the compound is of Formula II, wherein X is O and R10 is selected from C3-C6 cycloalkyl and linear or branched C1-C6 alkyl.
174. A method for controlling one or more insects, comprising exposing said one or more insects to a synergistic composition comprising a compound of Formula II′ or a compound of Formula III′, and a pyrethroid;
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
wherein the synergistic composition produces, when said one or more insects are exposed to the synergistic composition, a combined toxicant effect greater than the sum of the separate toxicant effects from the compound of Formula II′ or Formula III′ and the pyrethroid, at comparable concentrations.
175. The method of embodiment 174, wherein said toxicant effect is the vapor toxicity of the synergistic composition.
176. The method of embodiment 174 or 175, wherein the synergistic composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′ or Formula III′.
177. The method of any one of embodiments 174-176, wherein said synergistic composition comprises a compound of Formula II′ and transfluthrin.
178. The method of any one of embodiments 174-177, wherein X″ is O.
179. The method of any one of embodiments 174-178, wherein R6′ and R7′ are selected from halo or C1-C6 alkyl.
180. The method of any one of embodiments 174-179, wherein R8′ and R9′ are each independently C1-C3 alkyl.
181. The method of any one of embodiments 174-180, wherein R8′ and R9′ are each methyl.
182. The method of any one of embodiments 174-181, wherein said compound of Formula II is
183. The method of any one of embodiments 174-1181, wherein said composition comprises
and transfluthrin.
184. The method of any one of embodiments 174-183, wherein the synergistic composition is a solution, dust, granular formulation or emulsion.
185. The method of any one of embodiments 174-183, wherein the synergistic composition is a liquid solution or emulsion.
186. The method of any one of embodiments 174-185, wherein the synergistic composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′.
187. The method of any one of embodiments 174-186, wherein said one or more insects are flies, spiders, butterflies, crabs, mosquitos, centipedes, ticks, millipedes, or scorpions.
188. The method of any one of embodiments 174-186, wherein said one or more insects are mosquitos.
189. A composition comprising an essential oil, and a second compound selected from a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, or Formula VII, wherein the composition is synergistic, in intimate admixture with a carrier; or, comprising about 0.01-99.99% of an essential oil; and about 99.99-0.01% of a second compound selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, or Formula VII
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C2 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy,
wherein the composition is synergistic, in intimate admixture with a carrier.
190. The composition of embodiment 189, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, Canadian balsam, nutmeg oil, fennel oil, dill weed oil, balsam copaiba, and tea tree oil.
191. The composition of embodiment 189 or 190, wherein said essential oil is citronella oil.
192. The composition of embodiment 189, wherein said second compound is a pyrethroid.
193. The composition of any one of embodiments 189-192, wherein said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, empenthrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
194. The composition of any one of embodiments 189-193, wherein said pyrethroid is metofluthrin.
195. The composition of embodiment 189, wherein said composition comprises a pyrethroid, wherein said pyrethroid is metofluthrin and said essential oil is selected from the group consisting of citronella oil, Canadian balsam, galbanum oil, ginger root oil, dill seed oil, and cypress oil.
196. The composition of any one of embodiments 189-195, wherein said composition comprises metofluthrin having a concentration of about 0.1 μg/cm2, and said essential oil having a concentration selected from the group consisting of 100 μg/cm2, 30 μg/cm2, and 20 μg/cm2.
197. A method of repelling a species of insect from a locus to which said species of insect is normally attracted, comprising contacting on said locus a non-toxic effective insect repellent of an essential oil in an amount of about 0.01-99.99%, and a second compound selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, and Formula VII, wherein said second compound is present in an amount from 99.99-0.01%,
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein the composition is synergistic, in intimate admixture with a carrier.
198. The method of embodiment 197, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, Canadian balsam, nutmeg oil, fennel oil, dill weed oil, balsam copaiba, and tea tree oil.
199. The method of embodiment 197 or 198, wherein said essential oil is citronella oil.
200. The method of any one of embodiments 197-199, wherein said second compound is a pyrethroid.
201. The method of any one of embodiments 197-200, wherein said pyrethroid is selected from the group consisting of permethrin, empenthrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
202. The method of any one of embodiments 197-201, wherein said pyrethroid is metofluthrin.
203. The method of any one of embodiments 197-202, wherein said composition comprises a pyrethroid, wherein said pyrethroid is metofluthrin, and said essential oil is selected from the group consisting of citronella oil, Canadian balsam, galbanum oil, ginger root oil, dill seed oil, and cypress oil.
204. The method of any one of embodiments 197-203, wherein said composition comprises metofluthrin having a concentration of about 0.1 μg/cm2, and said essential oil having a concentration selected from the group consisting of 100 μg/cm2, 30 μg/cm2, and 20 μg/cm2.
205. The method of any one of embodiments 50-188 or 197-204, wherein said species of insect is not physically contacted with said locus.
206. A method of providing a composition of any one of embodiments 1-205 in an insect repellent medium from which a vaporized composition of any one of embodiments 1-205 can be dispersed.
208. The method of any one of embodiments 50-188 or 197-205, wherein the composition is formulated for use in a vaporizer, evaporator, fan, heat, candle, or wicked apparatus.
209. The method of any one of embodiments 197-204 or the composition comprising any one of embodiments 189-196, wherein said essential oil is citronella oil and said second compound is metofluthrin.
210. The method of any one of embodiments 197-204 or the composition comprising any one of embodiments 189-196, wherein said essential oil is citronella oil and said second compound is empenthrin.
211. A method of repelling an arthropod from an object or locus, comprising contacting on said object or locus a composition comprising a compound of Formula II′ or a compound of Formula III′:
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, nootkatone, DEET, benzyl benzoate, ethyl hexanediol, diethyl phthalate, diethyl carbate, geraniol, citronellol, citronellal, citral, oil of lemon eucalyptus, cinnamaldehyde, and VUAA-1,
wherein the composition is synergistic, in admixture with a carrier.
212. The method of embodiment 211, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, Canadian balsam, nutmeg oil, fennel oil, dill weed oil, balsam copaiba, and tea tree oil.
213. The method of embodiment 211 or 212, wherein said essential oil is citronella oil.
214. The method of embodiment 211, wherein said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, empenthrin, and transfluthrin.
215. The method of any one of embodiments 211-214, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′ or a compound of Formula III′.
216. The method of any one of embodiments 211-215, wherein the composition is a solution, dust, granular formulation or emulsion.
217. The method of any one of embodiments 211-216, wherein the composition is a liquid solution or emulsion.
218. The method of any one of embodiments 211-217, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′ or a compound of Formula III′.
219. The method of any one of embodiments 211-218, wherein said arthropod is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
220. The method of embodiment 219, wherein said arthropod is a mosquito.
221. The method of any one of embodiments 211-221, where the object or locus is an area, an environment, or the skin of an animal.
222. The method of any one of embodiments 211-221, wherein said composition comprises a compound of Formula II′.
223. The method of any one of embodiments 211-222, wherein X″ is O.
224. The method of any one of embodiments 211-223, wherein R8′ and R9′ are each C1-C6 alkyl.
225. The method of any one of embodiments 211-224, wherein R8′ and R9′ are each methyl.
226. The method of any one of embodiments 211-225, wherein R7′ and R6′ are each independently selected from halogen or C1-C6 alkyl.
227. The method of any one of embodiments 211-226, wherein said compound of Formula II′ is selected from
228. The method of any one of embodiments 211-227, wherein said composition comprises
and transfluthrin.
229. The method of any one of embodiments 211-228, wherein said composition comprises
and citronella oil.
230. A method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula IV, a compound of Formula V, or a compound of Formula VI
wherein Y is selected from the group consisting of O, NH, and S;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
a compound of Formula II′ or a compound of Formula III′
R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in admixture with a carrier.
231. The method of embodiment 230, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula VI.
232. The method of embodiment 230 or 231, wherein R18 is hydrogen.
233. The method of any one of embodiments 230-232, wherein R13, R14, R16, and R17 are each halo.
234. The method of any one of embodiments 230-233, wherein R13, R14, R16, and R17 are each fluoro.
235. The method of any one of embodiments 230-234, wherein R16 is selected from hydrogen or C1-C3 alkyl-alkoxy.
236. The method of any one of embodiments 230-235, wherein said compound of Formula VI is
237. The method of any one of embodiments 230-236, wherein said composition comprises a compound of Formula VI and a compound of Formula II′.
238. The method of any one of embodiments 230-237, wherein X″ is O.
239. The method of any one of embodiments 230-238, wherein R8′ and R9′ are each methyl.
240. The method of any one of embodiments 230-239, wherein R7′ and R6′ are each independently selected from halogen or C1-C6 alkyl.
241. The method of any one of embodiments 230-240, wherein said compound of Formula VI is
242. The method of any one of embodiments 230-241, wherein said composition comprises a compound of Formula VI of
and a compound of Formula II′ of
243. The method of any one of embodiments 230-243, wherein the composition is a solution, dust, granular formulation or emulsion.
244. The method of any one of embodiments 230-243, wherein the composition is a liquid solution or emulsion.
245. The method of any one of embodiments 230-244, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula IV, Formula V, or Formula VI.
246. The method of any one of embodiments 230-245, wherein said arthropod is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
247. The method of any one of embodiments 230-247, wherein said arthropod is a mosquito.
248. The method of any one of embodiments 230-247, wherein the object or locus is an area, an environment, or the skin of an animal.
249. A method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula VII
wherein R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, linear or branched C1-C6 alkyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy; and
a compound selected from the group consisting of an essential oil, a pyrethroid, methyl jasmonate, IR3535, 2-undecanone, picaridin, benzaldehyde, p-menthane-3,8-diol, alpha-terpineyl isovalerate, DEET, VUAA-1, nootkatone, a compound of Formula II′, a compound of Formula III′, a compound of Formula IV, a compound of Formula V, and a compound of Formula VI
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
Y is selected from the group consisting of O, NH, and S;
R11 is selected from the group consisting of hydrogen, alkenyl, alkynyl, C1-C6 alkyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkylalkyl, arylalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, haloalkyl, alkenyl, alkynyl, halo, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in admixture with a carrier.
250. The method of embodiment 249 wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula VII.
251. The method of embodiment 249 or 250, wherein R30, R31, R32, and R34 are each hydrogen.
252. The method of any one of embodiments 249-251, wherein R33 is
253. The method of any one of embodiments 249-252, wherein R40, R41, R42, R43, and R44 are each hydrogen.
254. The method of any one of embodiments 249-253, wherein M is O.
255. The method of any one of embodiments 249-254, wherein R28 is hydrogen.
256. The method of any one of embodiments 249-255, wherein said compound of Formula VII is
257. The method of any one of embodiments 249-256, wherein said composition comprises
and citronella oil.
258. The method of any one of embodiments 249-257, wherein said composition comprises
and a compound of Formula VI.
259. The method of any one of embodiments 249-259, wherein said composition comprises
260. The method of any one of embodiments 249-259, wherein said composition comprises
and a compound of Formula II′.
261. The method of any one of embodiments 249-260, wherein said composition comprises
262. The method of any one of embodiments 249-261, wherein said composition comprises
263. The method of any one of embodiments 249-262, wherein the composition is a solution, dust, granular formulation or emulsion.
264. The method of any one of embodiments 249-263, wherein the composition is a liquid solution or emulsion.
265. The method of any one of embodiments 249-264, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula VII.
266. The method of any one of embodiments 249-265, wherein said arthropod is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
267. The method of any one of embodiments 249-266, wherein said arthropod is a mosquito.
268. The method of any one of embodiments 249-267, where the object or locus is an area, an environment, or the skin of an animal.
269. A method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula I′
I′ and a compound of Formula II′ or a compound of Formula III′
wherein R1′ and R2′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R3′ and R4′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R5′ is selected from the group consisting of linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X′ is selected from the group consisting of O, NH, and S;
R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl,
wherein the composition is synergistic, in admixture with a carrier.
270. The method of embodiment 269, wherein the composition contains about 0.0001 to 100000 parts per million of a compound of Formula I′.
271. The method of embodiment 269 or 270, wherein R3′ and R4′ are each methyl.
272. The method of any one of embodiments 269-271, wherein X′ is O.
273. The method of any one of embodiments 269-272, wherein R5′ is linear or branched C1-C6 alkyl.
274. The method of any one of embodiments 269-273, wherein the composition is a solution, dust, granular formulation, or emulsion.
275. The method of any one of embodiments 269-274, wherein the composition is a liquid solution or emulsion.
276. The method of any one of embodiments 269-275, wherein the composition contains about 0.0001 to 100000 parts per million of the compound of Formula I′.
277. The method of any one of embodiments 269-276, wherein the composition contains a compound of Formula I′ and a compound of Formula II′.
278. The method of any one of embodiments 269-277, wherein X″ is O.
279. The method of any one of embodiments 269-278, wherein R6′ and R7′ are each independently selected from halo or C1-C6 alkyl.
280. The method of any one of embodiments 269-279, wherein R8′ and R9′ are each methyl.
281. The method of any one of embodiments 269-280, wherein the compound of Formula II″ is
282. The method of any one of embodiments 269-281, wherein the composition comprises a compound of Formula I′ and
283. The method of any one of embodiments 269-282, wherein the compound of Formula I′ is
284. The method of any one of embodiments 269-283, wherein said arthropod is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
285. The method of any one of embodiments 269-284, wherein said arthropod is a mosquito.
286. The method of any one of embodiments 269-285, where the object or locus is an area, an environment, or the skin of an animal.
287. A method for controlling one or more arthropods, comprising exposing said one or more arthropods to a synergistic composition comprising a compound of Formula II′ or a compound of Formula III′:
wherein R6′ and R7′ are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, or C3-C12 heterocycloalkyl;
R8′ and R9′ are each independently selected from hydrogen, haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
X″ is selected from the group consisting of O, NH, and S;
R21′, R22′, R23′, R24′, and R25′ are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P′ is selected from the group consisting of O, NH, and S;
R26′ is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl; and
a pyrethroid,
wherein the synergistic composition produces, when said one or more arthropods are exposed to the synergistic composition, a combined toxicant effect greater than the sum of the separate toxicant effects from the compound of Formula II′ or Formula III′ and the pyrethroid, at comparable concentrations.
288. The method embodiment 287, wherein said toxicant effect is the vapor toxicity of the synergistic composition.
289. The method of embodiment 287 or 288, wherein the synergistic composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′ or Formula III′.
290. The method of any one of embodiments 287-289, wherein said synergistic composition comprises a compound of Formula II′ and transfluthrin.
291. The method of any one of embodiments 287-290, wherein X″ is O.
292. The method of any one of embodiments 287-291, wherein R6′ and R7′ are selected from halo or C1-C6 alkyl.
293. The method of any one of embodiments 287-292, wherein R8′ and R9′ are each independently C1-C3 alkyl.
294. The method of any one of embodiments 287-293, wherein R8′ and R9′ are each methyl.
295. The method of any one of embodiments 287-294, wherein said compound of Formula II is
296. The method of any one of embodiments 287-295, wherein said composition comprises
and transfluthrin.
297. The method of any one of embodiments 287-296, wherein the synergistic composition is a solution, dust, granular formulation or emulsion.
298. The method of any one of embodiments 287-297, wherein the synergistic composition is a liquid solution or emulsion.
299. The method of any one of embodiments 287-298, wherein the synergistic composition contains about 0.0001 to 100000 parts per million of a compound of Formula II′.
300. The method of any one of embodiments 287-299, wherein said one or more arthropods are flies, spiders, butterflies, crabs, mosquitos, centipedes, ticks, millipedes, or scorpions.
301. The method of any one of embodiments 287-300, wherein said one or more arthropods are mosquitos.
302. A method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, or Formula VII
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C2 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, halo, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S; and
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy,
wherein the composition is synergistic, in admixture with a carrier.
303. The method of embodiment 302, wherein the composition is a solution, dust, granular formulation or emulsion.
304. The method of embodiment 302 or 303, wherein the composition is a liquid solution or emulsion.
305. The method of any one of embodiments 302-304 wherein said arthropod is a fly, spider, butterfly, crab, mosquito, centipede, tick, millipede, or scorpion.
306. The method of any one of embodiments 302-305, wherein said arthropod is a mosquito.
307. The method of any one of embodiments 302-306, wherein the mosquito is Aedes aegypti.
308. The method of any one of embodiments 302-307, where the object or locus is an area, an environment, or the skin of an animal.
309. The method of any one of embodiments 302-308, wherein said compound is of Formula II, wherein X is O and R10 is hydrogen.
310. The method of any one of embodiments 302-209, wherein R8 and R9 are each methyl.
311. The method of any one of embodiments 302-310, wherein said compound is selected from the group consisting of
312. The method of any one of embodiments 302-311, wherein said compound is of Formula III.
313. The method of any one of embodiments 302-312, wherein P is O and R27 is H.
314. The method of any one of embodiments 302-313, wherein R23 is halo and R21, R22, R24, and R25 are each hydrogen.
315. The method of any one of embodiments 302-314, wherein R23 is chloro.
316. The method of any one of embodiments 302-315, wherein said compound is
317. The method of any one of embodiments 302-316, wherein said compound is of Formula VI.
318. The method of any one of embodiments 302-317, wherein R13, R14, R16, and R17 are each halo.
319. The method of any one of embodiments 302-318, wherein R13, R14, R16, and R17 are each fluoro.
320. The method of any one of embodiments 302-319, wherein R15 is hydrogen.
321. The method of any one of embodiments 302-320, wherein R18 is hydrogen.
322. The method of any one of embodiments 302-321, wherein the compound of Formula VI is
323. The method of any one of embodiments 302-322, wherein the compound is of Formula IV.
324. The method of any one of embodiments 302-323, wherein Y is O.
325. The method of any one of embodiments 302-325, wherein R11 is CN.
326. The method of any one of embodiments 302-325, wherein the compound of Formula IV is
327. The method of any one of embodiments 302-327, wherein the compound is of Formula VII.
328. The method of any one of embodiments 302-327, wherein R30, R31, R32, and R34 are each hydrogen.
329. The method of any one of embodiments 302-328, wherein R33 is
330. The method of any one of embodiments 302-329, wherein R40, R41, R42, R43, and R44 are each hydrogen.
331. The method of any one of embodiments 302-330, wherein M is O.
332. The method of any one of embodiments 302-331, wherein R28 is H.
333. The method of any one of embodiments 302-332, wherein the compound of Formula VII is
334. The method of any one of embodiments 302-333, wherein the compound is of Formula II, wherein X is O and R10 is selected from C3-C6 cycloalkyl and linear or branched C1-C6 alkyl.
335. A composition comprising an essential oil; and a second compound selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, and Formula VII
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, alkoxy, halo, haloalkyl, alkenyl, alkynyl, C1-C6 alkyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy,
wherein the composition is synergistic, in admixture with a carrier.
336. The composition of embodiment 335, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, Canadian balsam, nutmeg oil, fennel oil, dill weed oil, balsam copaiba, and tea tree oil.
337. The composition of embodiment 335 or 336, wherein said essential oil is citronella oil.
338. The composition of any one of embodiments 335-337, wherein said second compound is a pyrethroid.
339. The composition of any one of embodiments 335-338, wherein said pyrethroid is selected from the group consisting of permethrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, empenthrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
340. The composition of any one of embodiments 335-339, wherein said pyrethroid is metofluthrin.
341. The composition of any one of embodiments 335-340, wherein said composition comprises a pyrethroid, wherein said pyrethroid is metofluthrin and said essential oil is selected from the group consisting of citronella oil, Canadian balsam, galbanum oil, ginger root oil, dill seed oil, and cypress oil.
342. The composition of embodiment 341, wherein said composition comprises metofluthrin having a concentration of about 0.1 μg/cm2, and said essential oil having a concentration selected from the group consisting of 100 μg/cm2, 30 μg/cm2, and 20 μg/cm2.
343. A method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a composition comprising an essential oil, and a second compound selected from the group consisting of a pyrethroid, a compound of Formula II, Formula III, Formula IV, Formula V, Formula VI, and Formula VII
wherein R6 and R7 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, C6-C12 heteroaryl, haloaryl, C6-C12 aryl, alkenyl, alkynyl, and C1-C3 alkyl; or
wherein R6′ and R7′ are taken together with the carbon to which they are attached to form a C6-C12 heteroaryl, C6-C12 aryl, C3-C12 cycloalkyl, haloaryl, or C3-C12 heterocycloalkyl;
R8 and R9 are each independently selected from hydrogen haloalkyl, alkenyl, alkynyl, and C1-C6 alkyl;
R10 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
X is selected from the group consisting of O, NH, and S;
R21, R22, R23, R24, and R25 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
P is selected from the group consisting of O, NH, and S;
R26 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R27 is selected from the group consisting of hydrogen, linear or branched C1-C12 alkyl, C3-C12 cycloalkyl, haloalkyl, alkenyl, alkynyl, C3-C12 cycloalkylalkyl, C6-C12 aryl, C6-C12 arylalkyl, C6-C12 heteroaryl, and C3-C12 heterocycloalkyl;
R11 is selected from the group consisting of hydrogen, C1-C6 alkyl, alkenyl, alkynyl, CN, halo, and haloalkyl;
R19 and R20 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, heteroarylalkyl, halo, and alkoxy, wherein said cycloalkyl, cycloalkylalkyl, arylalkyl, heterocycloalkyl, or heteroarylalkyl is optionally substituted with C1-C6 alkyl; or
where the substituents on R19 and R20, taken together with the carbon to which each is attached, form a C5-C7 cycloalkyl;
X1, X2, and X3 are each independently selected from the group consisting of CH, CH2, O, S, N, C═O, and NH; and
wherein at least one of X1, X2, and X3 is substituted with —COH;
R13, R14, R15, R16, and R17 are each independently selected from the group consisting of hydrogen, alkoxy, halo, C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, and C1-C3 alkyl-alkoxy;
R18 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, and linear or branched C1-C6 alkyl;
R28 is selected from the group consisting of hydrogen, haloalkyl, alkenyl, alkynyl, alkoxy, and C1-C6 linear or branched alkyl;
R30, R31, R32, R33, and R34 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy, and
wherein M is selected from the group consisting of O, NH, and S;
R40, R41, R42, R43, and R44 are each independently selected from the group consisting of hydrogen, linear or branched C1-C6 alkyl, haloalkyl, alkenyl, alkynyl, alkoxy, halo, cyano, hydroxy,
wherein the composition is synergistic, in admixture with a carrier.
344. The method of embodiment 343, wherein said essential oil is selected from the group consisting of citronella oil, Amyris oil, dill seed oil, galbanum oil, cade oil, ginger root oil, fir needle oil, guaiacwood oil, cypress oil, cinnamon bark oil, patchouli oil, cedarleaf oil, peppermint oil, lemongrass oil, orange oil, lavender oil, rosemary oil, cedarwood oil, lemon eucalyptus oil, catnip oil, geranium oil, castor oil, clove oil, soybean oil, basil oil, neem oil, vetiver oil, Canadian balsam, nutmeg oil, fennel oil, dill weed oil, balsam copaiba, and tea tree oil.
345. The method of embodiment 343 or 344, wherein said essential oil is citronella oil.
346. The method of any one of embodiments 343-345, wherein said second compound is a pyrethroid.
347. The method of any one of embodiments 343-346, wherein said pyrethroid is selected from the group consisting of permethrin, empenthrin, tetramethrin, metofluthrin, bifenthrin, kadethrin, allethrin, cyfluthrin, deltamethrin, cypermethrin, cyphenothrin, esfenvalerate, fenvalerate, flumethrin, tefluthrin, phenothrin, and transfluthrin.
348. The method of embodiments 343-347, wherein said pyrethroid is metofluthrin.
349. The method of any one of embodiments 343-348, wherein said composition comprises a pyrethroid, wherein said pyrethroid is metofluthrin, and said essential oil is selected from the group consisting of citronella oil, Canadian balsam, galbanum oil, ginger root oil, dill seed oil, and cypress oil.
350. The method of any one of embodiments 343-349, wherein said composition comprises metofluthrin having a concentration of about 0.1 μg/cm2, and said essential oil having a concentration selected from the group consisting of 100 μg/cm2, 30 μg/cm2, and 20 μg/cm2.
351. The method of any one of embodiments 343-350, or the composition of any one of embodiments 335-341, wherein said essential oil is citronella oil and said second compound is empenthrin.
352. The method of embodiment 351, wherein said composition comprises empenthrin having a concentration of about 0.1 μg/cm2, and said essential oil having a concentration of about 100 μg/cm2.
353. A method of repelling an arthropod from an object or locus, comprising contacting said object or locus with any single compound described herein, or a composition comprising any single compound and a carrier.
354. A method for controlling one or more arthropods, comprising exposing said one or more arthropods to any single compound described herein, or a composition comprising any single compound and a carrier.
355. A method of repelling an arthropod from an object or locus, comprising contacting said object or locus with a compound in Table 8, or a composition comprising a compound in Table 8 and a carrier.
356. A method for controlling one or more arthropods, comprising exposing said one or more arthropods to a compound in Table 8, or a composition comprising a compound in Table 8 and a carrier.
357. The method of any one of embodiments 211-356, wherein said arthropod is repelled from an adjacent area to said object or locus, wherein said arthropod is not physically contacted with said object or locus.
358. A method of providing a composition of any one of embodiments 1-357 in an arthropod repellent medium from which a vaporized composition of any one of embodiments 1-357 can be dispersed.
359. The method of any one of embodiments 1-358, wherein the composition is formulated for use in a vaporizer, evaporator, fan, heat, candle, or wicked apparatus.
360. The method of any one of embodiments 1-359, wherein the synergistic composition is a vapor.
361. The method or composition of any one of embodiments 1-360, wherein said arthropod is an insect.
362. The method of any one of embodiments 1-361, wherein said insect is repelled from an adjacent area to said object or locus, wherein said insect is not physically contacted with said object or locus.
363. A method of providing a composition of any one of embodiments 1-362 in an insect repellent medium from which a vaporized composition of any one of embodiments 1-362 can be dispersed.
The following examples are offered by way of illustration and not by way of limitation.
The following assay was conducted according to the procedures of Jiang et al., 2019 (Jiang S., Yang L, and Bloomquist J (2019) High-throughput screening method for evaluating spatial repellency and vapor toxicity to mosquitoes. Med. Vet. Entomol.). For assessing behavioral repellency (
As shown in
It was determined that the acid form of the compounds investigated was more active as spatial repellents than their respective parent compound, as shown in
The repellency of the pyrethroid acids additionally exhibited much less cross resistance in the PR Puerto Rico (pyrethroid-resistant) strain of Ae. aegypti, unlike their parent compounds. Table 1 shows one hr repellency EC50 values in g/cm2 for some pyrethroid acids. EC50 values were calculated from non-linear regression to a four parameter logistic equation (Prism, GraphPad Software, San Diego, Calif.) of the curves shown in
Table 2 displays the repellency EC50 in OR and PR (g/cm2) for several intact compounds, which exhibited significant vapor repellency.
As shown in Tables 1 and 2, the acids exhibited substantially more repellency compared to their corresponding intact parent compounds, most of which showed little or no activity except for transfluthrin and metofluthrin, which were designed to work in the vapor phase. Moreover, the spatial activity of pyrethrum was about equal to that of one of its components, TCA, against OR (Orlando) mosquitoes. Additionally, the cross resistance (RR) to the acids was much less.
Repellents/contact irritants were screened for synergism in mixtures containing an inactive level of TFA (50 μg/cm2)+EC20 treatment of test compound with the parentheses ( ) in
As shown in
Provided in Table 3 are the quantified repellency of standards that responded positively to the presence of 50 μg/cm2 of TFA after 1 hr. Citronella, methyl jasmonate, and 2-undecanone are natural products with insect repellent properties. EC50 values in μg/cm2 were determined as described in Table 1 and synergist ratios (SR) were calculated as EC50 compound alone/EC50 for compound+TFA. All compounds were synergized by TFA, with very large effects on VUAA-1 and permethrin.
a2-undecanone
a2-undecanone + TCA gave an EC50 of 7 μg/cm2 and a synergist ratio of 8.4.
A human bite protection assay was performed according to see if the repellency observed in glass tubes extended to bite protection. The assay was run in accordance with that of Tsikolia et al. (Tsikolia M, Bernier UR, Coy M, Chalaire K, Becnel J, Agramonte N, Tabanca N, Wedge D, Clark G, Linthicum K, Swale D, and J. R. Bloomquist J (2013) Insecticidal and fungicidal properties of novel trifluoromethylphenyl amides. Pestic. Biochem. Physiol. 107, 138-147). The results are provided in Table 4. Treated cloth patches were worn by human volunteers and the number of blood fed mosquitoes was determined after 1 min spent in a cage with 500 (±10%) female Ae. aegypti. Minimum Effective Dosage (MED in mg/cm2) is the minimum amount required to prevent 99% of bites in three human volunteers (UF IRB #201602334). Synergist ratio (SR)=MED chemical alone/MED chemical+TFA (0.047 mg/cm2) or TCA (0.094 mg/cm2). Thus, the synergism observed in the tube assays translated well to bite protection of human arms and was observed for both contact and spatial repellents.
It is generally known in the art that DEET can “trap” some odorants on surfaces (Syed Z and Leal W (2008) Mosquitoes smell and avoid the insect repellent DEET. Proc. Natl. Acad. Sci. USA 105: 13598-13603.). As such, experiments were performed to see if treating each half of a filter paper produced the same results as the mixture experiment in Example 3 (
The repellency of transfluthrin (TF) alone and when mixed with TFA was examined in
The synergistic interactions of TFA and citronella and transfluthrin (TF) and citronella were assessed in
Electroantennography (EAG) responses of OR (susceptible) and PR (resistant) strains of Ae. Aegypti were then obtained for TF, TFA, and TCA (
The manner in which Citronella synergizes VUAA-1, but not that of DEET was compared to TFA (
Pyrethroid alcohols were used to obtain repellency screening along and in combination with TFA (
Chemical analysis found that instability resulted in the rearrangement of GMR134 to its corresponding aldehyde. The aldehyde exhibited good repellency, as shown in
Because GMR 134 had good repellency and synergism with pyrethroid acids and citronella, it was tested in mixtures with pyrethroid alcohols (
It was next documented that different pyrethroid acids can synergize one another (
Table 5 shows EC50 values for repellency of experimental TFA esters in 1 hr exposures that displayed little knockdown at a screening concentration of 100 μg/cm2.
Screening results of TFA esters for synergism with citronella are provided in
The results of screening TFA esters for synergism with citronella are provided in
As shown in
Concentration-response curves for repellent mixtures of GMR 134 with and without TFA (50 μg/cm2) against OR and PR strains of Ae. Aegypti are provided in
Provided in
Table 8 shows the differential efficacy of benzaldehyde derivatives as both vapor active repellents and toxicants at screening concentrations. All data is reported as repellency ratios and percentage mortality at 24 hr. Fractions represent repellency as defined by Jiang et al. (Jiang S., Yang L, and Bloomquist J (2019). Med. Vet. Entomol.), where 0.5=0% repellency and 0=100% repellency. Numbers for 3-tert-butylbenzaldehyde and 3-chlorobenzaldehyde are % mortality, since they were rapidly lethal in 1 hr exposures.
Example 15: Synergism of Synthetic Pyrethroid Spatial Repellency and Vapor Toxicity with Essential Oils on Susceptible Orlando Ae. aegypti
Table 9 shows Synergism ratios of 24 hr vapor toxicity by plant essential oils (EO) at two concentrations; the repellency EC20 of each oil and at 100 μg/cm2, on Aedes aegypti adult female mosquitoes. Synergism ratio (SR)=LC50 pyrethroid/LC50 pyrethroid+EO.
The mortality of plant essential oils applied at various concentrations alone or in combination with 0.1 μg/cm2 in vapor toxicity assays on insecticide-susceptible Aedes aegypti (Orlando strain) females was investigated. The results are provided in
Next, the mortality of plant essential oils applied at various concentrations alone or in combination with 0.1 μg/cm2 in vapor toxicity assays on insecticide-susceptible Anopheles gambiae (G3 strain) females was investigated. The results are provided in
The vapor toxicity of metofluthrin alone and in combination with citronella oil (CO) on susceptible Orlando and pyrethroid-resistant Puerto Rico strains of Ae. aegypti was investigated. The results are provided in Table 10 and in
Next, the vapor toxicity of empenthrin applied to two strains of Aedes aegypti, the pyrethroid-susceptible Orlando and pyrethroid-resistant Puerto Rico strain, was investigated. The results are shown in
The title compound was prepared using General Method B from 1-pentanol (0.043 mL, 0.397 mmol), 1R-trans-permethrinic acid (0.12 g, 0.562 mmol), N,N-Dicyclohexylcarbodiimide (DCC) (0.102 g, 0.49 mmol), 4-Dimethylaminopyridine (DMAP) (8.6 mg, 0.07 mmol) and dichloromethane (DCM) (1.5 mL). Automated flash chromatography of the crude oil yielded the product as a clear oil (110.5 mg, 99% yield). 1H NMR (500 MHz, Chloroform-d) δ 5.62 (d, J=8.4 Hz, 1H), 4.08 (td, J=6.8, 3.9 Hz, 2H), 2.23 (dd, J=8.4, 5.3 Hz, 1H), 1.68-1.59 (m, 3H), 1.38-1.32 (m, 4H), 1.29 (s, 3H), 1.19 (s, 3H), 0.91 (t, J=7.1 Hz, 3H). 13C NMR (126 MHz, Chloroform-d) δ 171.10, 127.12, 121.84, 64.80, 34.85, 32.69, 28.68, 28.39, 28.06, 22.59, 22.31, 20.05, 13.94.
The title compound was prepared using General Method B from cyclopentanol (0.0426 mL, 0.469 mmol), 1R-trans-permethrinic acid (0.12 g, 0.562 mmol), DCC (0.102 g, 0.49 mmol), DMAP (8.6 mg, 0.07 mmol) and DCM (1.5 mL). Automated flash chromatography of the crude oil yielded the product as a clear oil (111.5 mg, 86%). 1H NMR (500 MHz, Chloroform-d) δ 5.61 (d, J=8.4 Hz, 1H), 5.17 (tt, J=5.9, 2.9 Hz, 1H), 2.21 (dd, J=8.4, 5.4 Hz, 1H), 1.87 (dddd, J=13.0, 8.0, 3.7, 1.5 Hz, 2H), 1.79-1.54 (m, 7H), 1.29 (s, 3H), 1.19 (s, 3H). 13C NMR (126 MHz, Chloroform-d) δ 170.84, 127.24, 121.75, 77.36, 35.13, 32.86, 32.69, 32.57, 28.63, 23.84-23.69 (m), 22.65, 20.05.
The title compound was prepared using General Method B from cyclobutanol (0.0367 mL, 0.469 mmol), 1R-trans-permethrinic acid (0.12 g, 0.562 mmol), DCC (0.102 g, 0.49 mmol), DMAP (8.6 mg, 0.07 mmol) and DCM (1.5 mL). Automated flash chromatography of the crude oil yielded the product as a clear oil (106.15 mg, 86% yield). 1H NMR (500 MHz, Chloroform-d) δ 5.61 (d, J=8.4 Hz, 1H), 4.99 (p, J=7.6 Hz, 1H), 2.36 (dtdd, J=11.3, 5.3, 2.7, 1.6 Hz, 2H), 2.22 (dd, J=8.4, 5.4 Hz, 1H), 2.14-2.03 (m, 2H), 1.81 (tddt, J=11.6, 9.0, 2.7, 1.3 Hz, 1H), 1.68-1.59 (m, 1H), 1.58 (d, J=5.3 Hz, 1H), 1.29 (s, 3H), 1.20 (s, 3H). 13C NMR (126 MHz, Chloroform-d) δ 170.40, 127.12, 121.86, 69.02, 34.77, 32.66, 30.45, 30.44, 28.79, 22.61, 20.00, 13.56.
The title compound was prepared using General Method B from cyclopropanol (0.0297 mL, 0.469 mmol), 1R-trans-permethrinic acid (0.12 g, 0.562 mmol), DCC (0.102 g, 0.49 mmol), DMAP (8.6 mg, 0.07 mmol) and DCM (1.5 mL). Automated flash chromatography of the crude oil yielded the product as a clear oil (94.9 mg, 81% yield). 1H NMR (500 MHz, Chloroform-d) δ 5.60 (d, J=8.3 Hz, 1H), 4.20-4.04 (m, 1H), 2.23 (dd, J=8.4, 5.3 Hz, 1H), 1.55 (d, J=5.3 Hz, 1H), 1.29 (s, 3H), 1.18 (s, 3H), 0.76-0.64 (m, 4H). 13C NMR (126 MHz, Chloroform-d) δ 171.88, 126.94, 122.03, 49.05, 34.60, 32.86, 29.01, 22.56, 19.98, 5.16, 5.12.
Prepared from the general procedure above (Method B) from 2,2,2-trifluoroethan-1-amine (0.0368 mL, 0.469 mmol), 1R-trans-permethrinic acid (0.12 g, 0.562 mmol), DCC (0.102 g, 0.49 mmol), DMAP (8.6 mg, 0.07 mmol) and DCM (1.5 mL). Automated flash chromatography of the crude oil yielded the product as a clear oil (112.78 mg, 83% yield). 1H NMR (500 MHz, Chloroform-d) δ 6.65 (t, J=6.5 Hz, 1H), 5.62 (d, J=8.2 Hz, 1H), 4.02-3.79 (m, 2H), 2.28 (dd, J=8.2, 5.2 Hz, 1H), 1.50 (d, J=5.2 Hz, 1H), 1.25 (s, 3H), 1.18 (s, 3H). 13C NMR (126 MHz, Chloroform-d) δ 170.37, 127.07, 122.97 (q, J=278.4 Hz), 121.99, 40.71 (q, J=34.7 Hz), 36.39, 31.46, 30.89, 22.57, 19.72.
Efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental errors and deviations should be accounted for.
One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practicing the subject matter described herein. The present disclosure is in no way limited to just the methods and materials described.
Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this subject matter belongs, and are consistent with: Singleton et al (1994) Dictionary of Microbiology and Molecular Biology, 2nd Ed., J. Wiley & Sons, New York, N.Y.; and Janeway, C., Travers, P., Walport, M., Shlomchik (2001) Immunobiology, 5th Ed., Garland Publishing, New York.
Throughout this specification and the claims, the words “comprise,” “comprises,” and “comprising” are used in a non-exclusive sense, except where the context requires otherwise. It is understood that embodiments described herein include “consisting of” and/or “consisting essentially of” embodiments.
Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit, unless the context clearly dictates otherwise, between the upper and lower limit of the range and any other stated or intervening value in that stated range, is encompassed. The upper and lower limits of these small ranges which may independently be included in the smaller rangers is also encompassed, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included.
Many modifications and other embodiments set forth herein will come to mind to one skilled in the art to which this subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.
This application claims the benefit of priority to U.S. Provisional Patent Application No. 62/880,503, filed on Jul. 30, 2019, the content of which is incorporated by reference herein in its entirety for all purposes.
This invention was made with government support under 58-0208-5-01 & 59-6036-8-001 awarded by The United States Department of Agriculture, Agriculture Research Services and under U01 CK000510 awarded by The United States Center for Disease Control. The government has certain rights in the invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2020/044292 | 7/30/2020 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 62880503 | Jul 2019 | US |
