Insect repellent compounds and compositions, and methods thereof

Abstract

The present invention relates to monoterpenoid and phenylpropanoid containing derivative compounds, methods of making the compounds, compositions comprising the compounds, and methods of repelling pests using the compounds and/or compositions.

What is claimed: 
     
         1 . A compound of formula (A) as follows: 
       
         
           
           
               
               
           
         
         wherein
 R 1  is a monoterpenoid or phenylpropanoid moiety; 
 R 2  is substituted or unsubstituted and is selected from the group consisting of H, C 1 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, aryl, heteroaryl, —(CH 2 ) n -heteroaryl, and C 3 -C 7  unbranched or branched cycloalkenyl; and
 n is an integer from 0-3, with the proviso that when R 1  is a monoterpenoid moiety R 2  is not a tert-butyl group. 
 
 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is a monoterpenoid moiety. 
     
     
         3 . The compound of  claim 2 , wherein the monoterpenoid moiety is selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1 , wherein R 1  is phenylpropanoid moiety. 
     
     
         5 . The compound of  claim 4 , wherein the phenylpropanoid moiety is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1 , wherein R 2  is H. 
     
     
         7 . The compound of  claim 1 , wherein R 2  is C 3 -C 7  branched alkyl selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 1 , wherein R 2  is C 2 -C 7  unbranched or branched alkenyl selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         9 . The compound of  claim 1 , wherein R 2  is C 3 -C 7  unbranched or branched alkynyl selected form the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 1 , wherein R 2  is C 3 -C 7  unbranched or branched cycloalkyl selected form the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 1 , wherein R 2  is: 
       
         
           
           
               
               
           
         
         wherein
 R 3  and R 4  are independently selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, vinyl, allyl, and propargyl. 
 
       
     
     
         12 . The compound of  claim 11 , wherein
 R 3  and R 4  are both H,   R 3  and R 4  are both CH 3 ,   R 3  is CH 3  and R 4  is H, or   R 3  is allyl and R 4  is H.   
     
     
         13 . The compound of  claim 1 , wherein R 2  is: 
       
         
           
           
               
               
           
         
         wherein
 R 3  is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, vinyl, allyl, and propargyl. 
 
       
     
     
         14 . The compound of  claim 1 , wherein the compound is selected from the group consisting of: menthyl cyclopropanecarboxylate, citronellyl isovalerate, citronellyl cyclopropanecarboxylate, thymyl cyclopropanecarboxylate, thymyl isovalerate, eugenyl isovalerate, carvacryl cyclopropanecarboxylate, carvacryl isovalerate, citronellyl formate, thymyl formate, carvacryl formate, thymyl cyclobutanecarboxylate, thymyl isobutyrate, eugenyl formate, eugenyl cyclopropanecarboxylate, eugenyl isobutyrate, eugenyl cyclobutanecarboxylate, eugenyl isovalerate, vanillin formate, vanillin cyclopropanecarboxylate, vanillin isobutyrate, vanillin cyclobutanecarboxylate, vanillin isovalerate, myrtenyl cyclopropanecarboxylate, geranyl cyclopropanecarboxylate, neryl cyclopropanecarboxylate, geranyl cyclobutanecarboxylate, neryl cyclobutanecarboxylate, citronellyl cyclobutanecarboxylate, linalyl isobutyrate, perillyl cyclopropanecarboxylate, perillyl cyclobutanecarboxylate, perillyl isobutyrate, perillyl isovalerate, cinnamyl cyclopropanecarboxylate, cinnamyl cyclobutanecarboxylate, linalyl cyclopropanecarboxylate, α-terpinyl cyclopropanecarboxylate, thymyl cyclohexanecarboxylate, thymyl cyclopentanecarboxylate, α-terpinyl cyclobutanecarboxylate, thymyl 3,3-dimethylacrylate, thymyl 1-methyl-1-cyclobutanecarboxylate, citronellyl 3,3-dimethylacrylate, citronellyl 1-methyl-1-cyclobutanecarboxylate, neryl 3,3-dimethylacrylate, neryl 1-methyl-1-cyclobutanecarboxylate, menthyl cyclobutanecarboxylate, perillyl cyclohexanecarboxylate, perillyl cyclopentanecarboxylate, menthyl cyclopentanecarboxylate, menthyl cyclohexanecarboxylate, menthyl 3,3-dimethylacrylate, citronellyl cyclopentanecarboxylate, fenchyl cyclopropanecarboxylate, fenchyl cyclobutanecarboxylate, fenchyl isovalerate, fenchyl formate, bornyl cyclopropanecarboxylate, bornyl cyclobutanecarboxylate, bornyl isovalerate, bornyl formate, isobornyl cyclopropanecarboxylate, isobornyl cyclobutanecarboxylate, isobornyl isovalerate, isobornyl formate, linalyl cyclobutanecarboxylate, linalyl isovalerate, linalyl formate, citronellyl tiglate, menthyl tiglate, thymyl tiglate, citronellyl thiophene-2-carboxylate, menthyl thiophene-2-carboxylate, thymyl thiophene-2-carboxylate, citronellyl levulinate, menthyl levulinate, thymyl levulinate, citronellyl 2-furoate, menthyl 2-furoate, thymyl 2-furoate, citronellyl benzoate, menthyl benzoate, thymyl benzoate, myrtenyl cyclobutanecarboxylate, carvacryl cyclobutanecarboxylate, citronellyl isobutyrate, carvacryl isobutyrate, geranyl cyclopentanecarboxylate, neryl cyclopentanecarboxylate, geranyl cyclohexanecarboxylate, neryl cyclohexanecarboxylate, menthyl 1-methyl-1-cyclobutanecarboxylate, 7-(2-methylpropanoyloxy)coumarin, 7-(3-methylbutanoyloxy)coumarin, 7-(cyclopropanecarboxoyloxy)coumarin, 7-(cyclobutanecarboxoyloxy)coumarin, 7-(cyclopentanecarboxoyloxy)coumarin, carvyl formate, carvyl isobutyrate, carvyl isovalerate, carvyl cyclopropanecarboxylate, carvyl cyclobutanecarboxylate, carvyl cyclopentanecarboxylate, cis-verbenyl cyclopropanecarboxylate, c/.s-verbenyl cyclobutanecarboxylate, cis-verbenyl cyclopentanecarboxylate, thymyl cyclopropylacetate, citronellyl cyclopropylacetate, menthyl cyclopropylacetate, thymyl thiophen-2-ylacetate, citronellyl thiophen-2-ylacetate, menthyl thiophen-2-ylacetate, cinnamyl isovalerate, geranyl isovalerate, neryl isovalerate, menthyl isovalerate, α-terpinyl isovalerate, myrtenyl isovalerate, cinnamyl isobutyrate, geranyl isobutyrate, neryl isobutyrate, menthyl isobutyrate, α-terpinyl isobutyrate, bomyl isobutyrate, isobornyl isobutyrate, fenchyl isobutyrate, myrtenyl isobutyrate, cis-verbenyl isobutyrate, menthyl formate, carvacryl cyclopentanecarboxylate, carvacryl cyclohexanecarboxylate, cis-verbenyl isovalerate, thymyl 2,2-dimethylcyclopropanecarboxylate, citronellyl 2,2-dimethylcyclopropanecarboxylate, menthyl 2,2-dimethylcyclopropanecarboxylate, thymyl trans-1,2-dimethyl cyclopropanecarboxylate, citronellyl trans-1,2-dimethyl cyclopropanecarboxylate, menthyl trans-1,2-dimethyl cyclopropanecarboxylate, thymyl 1-allylcyclobutanecarboxylate, citronellyl 1-allylcyclobutanecarboxylate, menthyl 1-allyl cyclobutanecarboxylate, thymyl 1-allyl cyclopropanecarboxylate, citronellyl 1-allyl cyclopropanecarboxylate, menthyl 1-allyl cyclopropanecarboxylate, thymyl 1-methyl cyclopropanecarboxylate, citronellyl 1-methyl cyclopropanecarboxylate, menthyl 1-methylcyclopropanecarboxylate, menthyl 1-methylcyclobutanecarboxylate, citronellyl difluoroacetate, citronellyl cyanoacetate, citronellyl hexanecarboxylate, citronellyl 2-fluoroisobutyrate, citronellyl 2,2-difluoropropanoate, citronellyl 3,3,3-trifluoropropanoate, citronellyl 3-oxocyclobutanecarboxylate, citronellyl 3-methylcyclobutanecarboxylate, citronellyl 3,3-difluorocyclobutanecarboxylate, thymyl 4-fluorobenzoate, 4-nitrothymyl cyclopropanecarboxylate, 4-bromothymyl cyclopropanecarboxylate, thymyl 2-fluoroisobutyrate, chlorothymyl isobutyrate, thymyl difluoroacetate, carvacryl 2-fluoroisobutyrate, and citronellyl chloroacetate. 
     
     
         15 . A compound of formula (B) as follows: 
       
         
           
           
               
               
           
         
         wherein
 R 5  is a monoterpenoid or phenylpropanoid moiety and 
 R 6  is substituted or unsubstituted and is selected from the group consisting of C 3 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, C 3 -C 7  unbranched or branched cycloalkenyl, C 3 -C 7  unbranched or branched heterocycle, C 2 -C 7  saturated or unsaturated hydroxyalkyl, and —(CR 11 R 12 ) p —O—(CR 11 R 12 ) q —OH; 
 R11 and R12 are individually selected from H or C 1-6  alkyl; 
 p is an integer from 1 to 4; and 
 q is an integer from 1 to 4, with the proviso that the compound is not selected from the group consisting of 
 
       
       
         
           
           
               
               
           
         
       
     
     
         16 . The compound of  claim 15 , wherein R 6  is: 
       
         
           
           
               
               
           
         
         wherein
 R 3  and R 4  are independently selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, vinyl, allyl, and propargyl. 
 
       
     
     
         17 . The compound of  claim 16 , wherein
 R 3  and R 4  are both H,   R 3  and R 4  are both CH 3 ,   R 3  is CH 3  and R 4  is H, or   R 2  is allyl and R 4  is H.   
     
     
         18 . The compound of  claim 15 , wherein R 6  is: 
       
         
           
           
               
               
           
         
         wherein
 R 3  is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, vinyl, allyl, and propargyl. 
 
       
     
     
         19 . The compound of  claim 15 , wherein R 6  is: 
       
         
           
           
               
               
           
         
         wherein
 n is from 1-4. 
 
       
     
     
         20 . The compound of  claim 19 , wherein n is 2. 
     
     
         21 . The compound of  claim 15 , wherein R 6  is C 3 -C 7  unbranched or branched alkyl selected from the group consisting of methyl, ethyl, propyl, isopropyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, 1,1-dimethylpropyl, and 1,2-dimethylpropyl. 
     
     
         22 . The compound of  claim 15 , wherein R 6  is C 2 -C 7  unbranched or branched alkenyl selected from the group consisting of allyl, propargyl, prenyl, and isoprenyl. 
     
     
         23 . The compound of  claim 15 , wherein R 6  is C 3 -C 7  unbranched or branched cycloalkyl selected from the group consisting of cyclobut-1-en-1-yl, cyclobut-2-en-1-yl, cyclopent-1-en-1-yl, cyclopent-2-en-1-yl, cyclopent-3-en-1-yl, and 1-methyl cy cl op ent-3-en-1-yl. 
     
     
         24 . The compound of  claim 15 , wherein R 6  is an C 3 -C 7  unbranched or branched cycloalkenyl, including cyclobut-1-en-1-yl, cyclobut-2-en-1-yl, cyclopent-1-en-1-yl, cyclopent-2-en-1-yl, cyclopent-3-en-1-yl, or 1-methylcyclopent-3-en-1-yl. 
     
     
         25 . The compound of  claim 15 , wherein R 5  is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         26 . The compound of  claim 15 , wherein R 5  is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         27 . The compound of  claim 15 , wherein R 5  is a substituted cinnamic acid. 
     
     
         28 . The compound of  claim 27 , wherein R 5  is: 
       
         
           
           
               
               
           
         
         wherein
 R 7  is selected from the group consisting of H, OH, OMe, and OEt. 
 
       
     
     
         29 . The compound of  claim 15 , wherein R 5  has a structure 
       
         
           
           
               
               
           
         
         wherein
 R 8  is selected from the group consisting of OH, OMe, and OEt; 
 R 9  is selected from the group consisting of H, OH, and OMe; and 
 R 10  is selected from the group consisting of H, OH, and OMe. 
 
       
     
     
         30 . The compound of  claim 29 , wherein R 5  is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         31 . The compound of  claim 15 , wherein the compound is selected from the group consisting of 2-hydroxyethyl citronellate, 2-hydroxyethyl cinnamate, cyclopropylmethyl geranate, cyclobutylmethyl citronellate, cyclopropylmethyl citronellate, cyclopropylmethyl cinnamate, cyclobutylmethyl cinnamate, 2-hydroxypropyl cinnamate, 3-hydroxypropyl cinnamate, 2-hydroxypropyl geranate, 3-hydroxypropyl geranate, 2-hydroxypropyl citronellate, 3-hydroxypropyl citronellate, cyclopentyl citronellate, tert-butyl citronellate, isoprenyl citronellate, prenyl citronellate, tert-prenyl citronellate, 2-hydroxyethyl geranate, 1,1-dimethylpropargyl citronellate, (3-methyloxetan-3-yl) methyl citronellate, 3-oxetanyl citronellate, 2-hydroxybut-1-ylcitronellate, 2-hydroxybut-1-yl geranate, 2-hydroxybut-1-yl cinnamate, 3-hydroxybut-2-yl citronellate, 3-hydroxybut-2-yl geranate, 3-hydroxybut-2-yl cinnamate, 4-hydroxybut-1-yl citronellate, 4-hydroxybut-1-yl geranate, 4-hydroxybut-1-yl cinnamate, (1-(hydroxymethyl)cyclopropyl)methyl citronellate, (1-(hydroxymethyl)cyclopropyl)methyl geranate, (1-(hydroxymethyl)cyclopropyl)methyl cinnamate, 3-hydroxy-2,2-dimethylpropyl citronellate, 3-hydroxy-2,2-dimethylpropyl geranate, 3-hydroxy-2,2-dimethylpropyl cinnamate, 4-hydroxycyclohexyl citronellate, 4-hydroxycyclohexyl geranate, and 4-hydroxycyclohexyl cinnamate. 
     
     
         32 . A method of making a compound of formula (A) or formula (B), (i) said method of making the compound of formula (A) comprising:
 reacting   (I) R 1 —OH with R 2 —COOH;   (II) R 1 —OH with   
       
         
           
           
               
               
           
         
          in the presence of a base; or 
         (III) R 1 —OH with 
       
       
         
           
           
               
               
           
         
       
       under conditions effective to form an ester having a structure of formula (A) 
       
         
           
           
               
               
           
         
         wherein
 R 1  is a monoterpenoid or phenylpropanoid moiety; 
 R 2  is substituted or unsubstituted and is selected from the group consisting of H, C 1 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, aryl, heteroaryl, —(CH 2 ) n -heteroaryl, and C 3 -C 7  unbranched or branched cycloalkenyl; n is an integer from 0-3; and 
 n is an integer from 0-3; and 
 X is a halide; or 
 
         (ii) said method of making the compound of formula (B) comprising
 reacting 
 (I) R 5 —COOH with R 6 —OH; 
 (II) 
 
       
       
         
           
           
               
               
           
         
          with R 2 —OH in the presence of a base; or 
          (III) 
       
       
         
           
           
               
               
           
         
          with R 6 —OH 
       
       under conditions effective to form an ester having a structure of Formula (B) 
       
         
           
           
               
               
           
         
         wherein
 R 5  is a monoterpenoid or phenylpropanoid moiety and 
 R 6  is substituted or unsubstituted and is selected from the group consisting of C 3 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, C 3 -C 7  unbranched or branched cycloalkenyl, C 3 -C 7  unbranched or branched heterocycle, C 2 -C 7  saturated or unsaturated hydroxyalkyl, and —(CR 11 R 12 ) p —O—(CR 11 R 12 ) q —OH; 
 R 11  and R 12  are individually selected from H or C 1-6  alkyl; 
 p is an integer from 1 to 4; 
 q is an integer from 1 to 4; and 
 X is a halide. 
 
       
     
     
         33 . The method of  claim 32 , wherein the base is selected from the group consisting of triethylamine, pyridine, diisopropylethylamine, and 4-dimethylaminopyridine. 
     
     
         34 . The method of  claim 32 , wherein said reacting is carried out in the presence of a catalyst or an acid catalyst. 
     
     
         35 . The method of  claim 34 , wherein said reacting is carried out in the presence of a catalyst selected from the group consisting of 4-dimethylaminopyridine, sulfuric acid, phosphoric acid, p-Moluenesulfonic acid, and polyphosphoric acid. 
     
     
         36 . The method of  claim 34 , wherein said reacting is carried out in the presence of an acid catalyst selected from the group consisting of sulfuric acid, phosphoric acid, p-Moluenesulfonic acid, and polyphosphoric acid. 
     
     
         37 . The method of  claim 32 , wherein said reacting is carried out in the presence of a coupling reagent and a catalyst. 
     
     
         38 . The method of  claim 37 , wherein the coupling reagent is selected from the group consisting of N,N′-dicyclohexylcarbodiimide; N,N′-diisopropylcarbodiimide; and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and the catalyst is 4-dimethylaminopyridine. 
     
     
         39 . A composition comprising:
 a carrier and   (i) a compound of formula (A) as follows:   
       
         
           
           
               
               
           
         
         wherein
 R 1  is a monoterpenoid or phenylpropanoid moiety and; 
 R 2  is substituted or unsubstituted and is selected from the group consisting of H, C 1 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, aryl, heteroaryl, —(CH 2 ) n -heteroaryl, and C 3 -C 7  unbranched or branched cycloalkenyl; and 
 n is an integer from 0-3, with the proviso that when R 1  is a monoterpenoid moiety R 2  is not a tert-butyl group; or
 (ii) a compound of formula (B) as follows: 
 
 
       
       
         
           
           
               
               
           
         
         wherein
 R 5  is a monoterpenoid or phenylpropanoid moiety and 
 R 6  is substituted or unsubstituted and is selected from the group consisting of C 3 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, C 3 -C 7  unbranched or branched cycloalkenyl, C 3 -C 7  unbranched or branched heterocycle, C 2 -C 7  saturated or unsaturated hydroxyalkyl, and —(CR 11 R 12 ) p —O—(CR 11 R 12 ) q —OH; 
 R 11  and R 12  are individually selected from H or C 1-6  alkyl; 
 p is an integer from 1 to 4; and 
 q is an integer from 1 to 4, with the proviso that the compound is not selected from the group consisting of 
 
       
       
         
           
           
               
               
           
         
       
     
     
         40 . The composition of  claim 39 , wherein the compound is in a substantially pure form. 
     
     
         41 . The composition of  claim 39 , wherein the compound is a single enantiomer or diastereomer. 
     
     
         42 . The composition of  claim 39 , wherein the compound is in a racemic or diastereomeric mixture. 
     
     
         43 . The composition of  claim 39 , wherein the carrier is selected from a solid, liquid, and gas. 
     
     
         44 . The composition of  claim 39 , wherein the composition is in the form of a lotion, spray, or cream. 
     
     
         45 . The composition of  claim 39  further comprising:
 a fragrance, perfume, or cologne. 
 
     
     
         46 . A method of repelling a pest, said method comprising:
  applying to a target area a composition comprising a compound of formula (A) or a compound of formula (B);   wherein, in the compound of formula (A),   
       
         
           
           
               
               
           
         
         R 1  is a monoterpenoid or phenylpropanoid moiety; 
         R 2  is substituted or unsubstituted and is selected from the group consisting of H, C 1 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, aryl, heteroaryl, —(CH 2 ) n -heteroaryl, and C 3 -C 7  unbranched or branched cycloalkenyl; and 
         n is an integer from 0-3, with the proviso that when R 1  is a monoterpenoid moiety R 2  is not a tert-butyl group; 
         wherein, in the compound of formula (B), 
       
       
         
           
           
               
               
           
         
         R 5  is a monoterpenoid or phenylpropanoid moiety; 
         R 6  is substituted or unsubstituted and is selected from the group consisting of C 3 -C 7  unbranched or branched alkyl, C 2 -C 7  unbranched or branched alkenyl, C 3 -C 7  unbranched or branched alkynyl, C 3 -C 7  unbranched or branched cycloalkyl, C 3 -C 7  unbranched or branched cycloalkenyl, C 3 -C 7  unbranched or branched heterocycle, C 2 -C 7  saturated or unsaturated hydroxyalkyl, and —(CR 11 R 12 ) p —O—(CR 11 R 12 ) q —OH; 
         R 11  and R 12  are individually selected from H or C 1-6  alkyl; 
         p is an integer from 1 to 4; and 
         q is an integer from 1 to 4; and 
         wherein said applying is carried out under conditions effective to repel a pest. 
       
     
     
         47 . The method of  claim 46 , wherein said applying is carried out with a vapor-delivery system. 
     
     
         48 . The method of  claim 46 , wherein the pest is selected from the group consisting of blood-sucking insects, biting insects, cockroaches, mosquitoes, blackfly, fleas, house flies, bam fly, face fly, bush fly, deer fly, horse fly, gnats, beetle, beer bug, louse, bed bug, earwig, ant, aphid, spruce bud worm, corn borer, sand flea, tsetse fly, assassin bug, biting flies, sand fly, stored grain pests, clothes moths, ticks, mites, spiders, phytophagous pests, and hematophagous pests.