US 20170208806A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0208806 A1 Barton et al. (43) Pub. Date: Jul. 27, 2017

(54) MOLECULES HAVING PESTICIDAL Publication Classification UTILITY, AND INTERMEDIATES, (51) Int. Cl. COMPOSITIONS, AND PROCESSES, AOIN 4I/O (2006.01) RELATED THERETO AOIN 37/34 (2006.01) AOIN 37/20 (2006.01) (71) Applicant: Dow AgroSciences LLC, Indianapolis, C07C 31 7/28 (2006.01) IN (US) C07C32L/4 (2006.01) (52) U.S. Cl. (72) Inventors: Thomas Barton, Indianapolis, IN (US); CPC ...... A0IN 41/10 (2013.01); C07C317/28 Xin Gao, Carmel, IN (US); Jim (2013.01); C07C321/14 (2013.01); A0IN Hunter, Indianapolis, IN (US); Paul R. 37/20 (2013.01); A0IN 37/34 (2013.01) LePlae, Brownsburg, IN (US); William (57) ABSTRACT C. Lo, Fishers, IN (US); Joshodeep This disclosure relates to the field of molecules having Boruwa, Noida, IN (US); Raghuram pesticidal utility against pests in Phyla Arthropoda, Mol Tangirala, Bengaluru, IN (US); Gerald lusca, and Nematoda, processes to produce Such molecules, B. Watson, Zionsville, IN (US); John intermediates used in Such processes, compositions contain Herbert, Fishers, IN (US) ing Such molecules, and processes of using Such molecules and compositions against Such pests. These molecules and compositions may be used, for example, as , (73) Assignee: Dow AgroSciences LLC, Indianapolis, , miticides, molluscicides, and nematicides. This IN (US) document discloses molecules having the following formula (“Formula One”).

(21) Appl. No.: 15/408,693

(22) Filed: Jan. 18, 2017

Related U.S. Application Data (60) Provisional application No. 62/286.684, filed on Jan. 25, 2016, provisional application No. 62/286,690, filed on Jan. 25, 2016. US 2017/020880.6 A1 Jul. 27, 2017

MOLECULES HAVING PESTCDAL diseases. While only a few dozen species of gastropods are UTILITY. AND INTERMEDIATES, serious regional pests, a handful of species are important COMPOSITIONS, AND PROCESSES, pests on a worldwide scale. In particular, gastropods affect RELATED THERETO a wide variety of agricultural and horticultural crops, such as, arable, pastoral, and fiber crops; vegetables; bush and CROSS REFERENCE TO RELATED tree fruits; herbs; and ornamentals (Speiser). APPLICATIONS 0007 cause damage to all types of private and 0001. This application claims the benefit of, and priority public structures, as well as, to agricultural and forestry from, U.S. Provisional Patent Application Ser. Nos. 62/286, resources. In 2005, it was estimated that termites cause over 684 and 62/286,690 both filed Jan. 25, 2016, each of which USS50 billion in damage worldwide each year (Korb). are expressly incorporated by reference herein. 0008 Consequently, for many reasons, including those mentioned above, there is an on-going need for the costly FIELD OF THIS DISCLOSURE (estimated to be about USS256 million per in 0002. This disclosure relates to the field of molecules 2010), time-consuming (on average about 10 years per having pesticidal utility against pests in Phyla Arthropoda, pesticide), and difficult, development of new Mollusca, and Nematoda, processes to produce Such mol (CropLife America). ecules, intermediates used in Such processes, pesticidal 0009. DeMassey et al. discloses the following structure. compositions containing Such molecules, and processes of For more detail, refer to U.S. 2002/0068838. using such pesticidal compositions against Such pests. These pesticidal compositions may be used, for example, as aca ricides, insecticides, miticides, molluscicides, and nemati cides. b X Z X S2Y N /R BACKGROUND OF THIS DISCLOSURE -C-N 0003 “Many of the most dangerous human diseases are C e 21 R2 transmitted by vectors” (Rivero et al.). “Historically, malaria, dengue, yellow fever, plague, filariasis, louse-borne d typhus, trypanosomiasis, leishmaniasis, and other vector borne diseases were responsible for more human disease and death in the 17" through the early 20" centuries than all CERTAIN REFERENCES CITED IN THIS other causes combined' (Gubler). Vector-borne diseases are DISCLOSURE responsible for about 17% of the global parasitic and infec tious diseases. Malaria alone causes over 800,000 deaths a 0010 CropLife America, The Cost of New Agrochemical year, 85% of which occur in children under five years of age. Product Discovery, Development & Registration, and Each year there are about 50 to about 100 million cases of Research & Development predictions for the Future, dengue fever. A further 250,000 to 500,000 cases of dengue 2010. hemorrhagic fever occur each year (Matthews). Vector con 0011 Gubler, D., Resurgent Vector-Borne Diseases as a trol plays a critical role in the prevention and control of Global Health Problem, Emerging Infectious Diseases, infectious diseases. However, resistance, includ Vol. 4, No. 3, p. 442-450, 1998. ing resistance to multiple insecticides, has arisen in all insect (0012 Korb, J., Termites, Current Biology, Vol. 17, No. species that are major vectors of human diseases (Rivero et al.). Recently, more than 550 pest species have 23, 2007. developed resistance to at least one pesticide (Whalon et al.). 0013 Matthews, G., Integrated Vector Management: 0004 Each year , plant pathogens, and weeds, Controlling Vectors of Malaria and Other Insect Vector destroy more than 40% of all food production. This loss Borne Diseases, Ch. 1, p. 1-2011. occurs despite the application of pesticides and the use of a 0014 Nicol, J., Turner S.; Coyne, L.; den Nijs, L., wide array of non-chemical controls. Such as, crop rotations, Hocksland, L., Tahna-Maafi, Z., Current Nematode and biological controls. If just some of this food could be Threats to World Agriculture, Genomic and Molecular saved, it could be used to feed the more than three billion Genetics of Plant Nematode Interactions, p. 21-43, people in the world who are malnourished (Pimental). 2011). 0005 Plant parasitic nematodes are among the most (0015 Pimental, D., in World Agriculture, widespread pests, and are frequently one of the most insidi Agricultural Sciences Vol. II, 2009. ous and costly. It has been estimated that losses attributable to nematodes are from about 9% in developed countries to 0016 Rivero, A., Vezilier, 3., Weill, M., Read, A., Gan about 15% in undeveloped countries. However, in the don, S., Insect Control of Vector-Borne Diseases: When is United States of America a survey of 35 States on various Insect Resistance a Problem? Public Library of Science crops indicated nematode-derived losses of up to 25% Pathogens, Vol. 6, No. 8, p. 1-9, 2010. (Nicol et al.). 0017 Speiser, B., Molluscicides, Encyclopedia of Pest 0006. It is noted that gastropods (slugs and snails) are Management, Ch. 219, p. 506-508, 2002. pests of less economic importance than other or 0018 Whalon, M., Mota-Sanchez, D., Hollingworth, R., nematodes, but in certain places they may reduce yields Analysis of Global Pesticide Resistance in Arthropods, substantially, severely affecting the quality of harvested Global Pesticide Resistance in Arthropods, Ch. 1, p. 5-33, products, as well as, transmitting human, , and plant 2008. US 2017/020880.6 A1 Jul. 27, 2017

DEFINITIONS USED IN THIS DISCLOSURE benoxacor, benoxafos, benquinox, benSulfuron, , 0019. The examples given in these definitions are gener bensultap, bentaluron, bentazon, bentaZone, benthiavalicarb, ally non-exhaustive and must not be construed as limiting benthiazole, benthiocarb, bentranil, benzadox, benzalko the disclosure. It is understood that a substituent should nium chloride, benzamacril, benzamizole, benzamorf, ben comply with chemical bonding rules and steric compatibility Zene hexachloride, benzfendizone, benzimine, benzipram, constraints in relation to the particular molecule to which it benzobicyclon, benzoepin, benzofenap, benzofluor, benzo is attached. These definitions are only to be used for the hydroxamic acid, benzomate, benzophosphate, benzothiadi purposes of this disclosure. azole, benzovindiflupyr, benzoximate, benzoylprop, benz 0020 “Active ingredient’ means a material having activ thiazuron, benzuocaotong, , benzyladenine, ity useful in controlling pests, and/or that is useful in helping berberine, beta-, beta-, bethoxazin, other materials have better activity in controlling pests, BHC, bialaphos, bicyclopyrone, bifenazate, bifenox, bifen examples of Such materials include, but are not limited to, thrin, bifujunzhi, bilanafos, binapacryl, bingqingxiao, bio acaricides, algicides, avicides, bactericides, fungicides, her allethrin, bioethanomethrin, biopermethrin, bioresmethrin, bicides, insecticides, molluscicides, nematicides, rodenti biphenyl, bisazir, bismerthiazol, bismerthiazol-copper, bis cides, virucides, antifeedants, bird repellents, chemosteri phenylmercury methylenediCX-naphthalene-y-Sulphonate), lants, herbicide Safeners, insect attractants, insect repellents, bispyribac, bistrifluron, bisultap, bitertanol, bithionol, bix repellents, mating disrupters, plantactivators, plant afen, blasticidin-S, borax, Bordeaux mixture, , growth regulators, and synergists. Specific examples of Such boscalid, BPPS, brassinolide, brassinolide-ethyl, brevi materials include, but are not limited to, the materials listed comin, , brofenprox, brofenvalerate, brofla in active ingredient group alpha. nilide, brofluthrinate, bromacil, , bromchlo 0021 “Active ingredient group alpha' (hereafter phos, , bromethrin, bromfenvinfos, “AIGA) means collectively the following materials: bromoacetamide, bromobonil, bromobutide, bromociclen, 0022 (1) (3-ethoxypropyl)mercury bromide, 1,2-dibro bromocyclen, bromo-DDT, bromofenoximrin, bromofos, moethane, 1,2-dichloroethane, 1,2-dichloropropane, 1,3-di bromomethane, bromophos, bromophos-ethyl, bromopropy chloropropene, 1-MCP, 1-methylcyclopropene, 1-naphthol, late, bromothalonil, bromoxynil, brompyrazon, bromucon 2-(octylthio)ethanol, 2.3.3-TPA, 2,3,5-tri-iodobenzoic acid, azole, bronopol, BRP BTH, bucarpolate, bufencarb, bumin 2,3,6-TBA, 2,4,5-T 2,4,5-TB, 2,4,5-TP, 2,4-D, 2,4-DB, 2,4- afos, bupirirnate, , Burgundy mixture, buSulfan, DEB, 2,4-DEP, 2,4-DES, 2,4-DP, 2,4-MCPA, 2,4-MCPB, busulphan, butacarb, butachlor, butafenacil, butam, butami 2iP. 2-methoxyethylmercury chloride, 2-phenylphenol, 3,4- fos, butane-, butathiofos, butenachlor, butene-fipro DA, 3,4-DB, 3,4-DP. 3,6-dichloropicolinic acid, 4-amin nil, butethrin, buthidazole, buthiobate, buthiuron, butifos, opyridine, 4-CPA, 4-CPB, 4-CPP 4-hydroxyphenethyl alco , butonate, butopyronoxyl, butoxycarboxinm, hol, 8-hydroxyquinoline Sulfate, butralin, butrizol, butroxydirm, buturon, butylamine, buty 8-phenylmercurioxyquinoline, abamectin, abamectin-amin late, butylchlorophos, butylene-fipronil, cacodylic acid, omethyl, abscisic acid, ACC, , acequinocyl, acet cadusafos, cafenstrole, calciferol, , calcium amiprid, acethion, acetochlor, acetofenate, acetophos, aceto chlorate, calcium cyanamide, calcium , calcium prole, acibenzolar, acifluorfen, aclonifen, ACN, acrep, polysulfide, calvinphos, cambendichlor, camphechlor, cam , acrolein, acrylonitrile, acy petacs, afidopyropen, phor, captafol, captan, carbam, carbamorph, carbanolate, , alachlor, alanap, alanycarb, albendazole, aldi carbaril, , carbasulam, carbathion, carbendazim, car carb, Sulfone, aldimorph, aldoxycarb, , bendaZol, carbetamide, carbofenotion, , carbon allethrin, allicin, allidochlor, allosamidin, alloxydim, allyl disulfide, , carbonyl sulfide, carbophe alcohol, allyxycarb, alorac, alpha-cypermethrin, alpha-en nothion, carbophos, , carboxazole, carboxide, dosulfan, alphamethrin, altretamine, , carboxin, carfentraZone, carpropamid, cartap, carvacrol, car aluminum phosphide, ametoctradin, ametridione, ametryn, vone, CAVP, CDAA, CDEA, CDEC, cellocidin, CEPC, ametryne, amibuzin, amicarbazone, amicarthiazol, amidi ceralure, cerenox, cevadilla, Cheshunt mixture, chinalphos, thion, amidoflumet, amidosulfuron, , aminocyc chinalphos-methyl, chinomethionat, chinomethionate, chi lopyrachlor, aminopyralid, aminotriazole, amiprofos ralaxyl, chitosan, chlobenthiaZone, chlomethoxyfen, chlo methyl, amiprophos, amiprophos-methyl, amisulbrom, ralose, chloramben, chloramine phosphorus, chlorampheni amiton, , amitrole, ammonium sulfamate, amobam, col, chloraniformethan, chloranil, chloranocryl, amorphous silica gel, amorphous silicon dioxide, ampropy , chlorazifop, chlorazine, chlorbenside, lfos, AMS, , ancymidol, anilazine, anilofos, ani chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, Suron, anthraquinone, antu, apholate, aramite, arprocarb, , , , chlorempenthrin, arsenous oxide, asomate, aspirin, asulam, athidathion, atra chloretazate, chlorethephon, , chloreturon, ton, atrazine, aureofungin, avermectin B1, AVG, aviglycine, chlorfenac, chlorfeinapyr, chlorfenazole, chlorfenethol, chlo aZaconazole, , azafenidin, , azidi rfenidim, chlorfemprop, chlorfenson, chlorfensulphide, chlo thion, azimsulfuron, azinphosethyl, azinphos-ethyl, azin rfenvinphos, -methyl, chlorfluaZuron, chlo phosmethyl, azinphos-methyl, aziprotryn, aziprotryne, rflurazole, chlorflurecol, chlorfluren, chlorflurenol, azithiram, azobenzene, azocyclotin, azothoate, aZOX chloridazon, chlorimuron, chlorinate, chlor-IPC, chlorme ystrobin, bachmedesh, barban, barbanate, barium hexafluo phos, chlormeduat, chlormesulone, chlormethoxynil, chlo rosilicate, barium polysulfide, barium silicofluoride, bar rinidine, chlornitrofen, chloroacetic acid, chlorobenzilate, thrin, basic copper carbonate, basic copper chloride, basic chlorodinitronaphthalenes, chlorofenizon, chloroform, chlo copper sulfate, BCPC, beflubutamid, benalaxyl, benalaxyl romebuform, chloromethiuron, chloroneb, , M. benazolin, bencarbazone, benclothiaz, bendaqingbing chlorophos, chloropicrin, chloropon, chloropropylate, chlo Zhi, , bendioxide, benefin, benfluralin, benfuriac rothalonil, chlorotoluron, chloroxifenidim, chloroxuron, arb, benfuresate, benmihuangcaoan, benodanil, benomyl. chloroxynil, chlorphonium, chlorphoxim, chlorpraZophos, US 2017/020880.6 A1 Jul. 27, 2017 chlorprocarb, chlorpropham, , chlorpyrifos thoate, dimethomorph, dirnethrin, dimethyl carbate, methyl, chlorquinox, chlorSulfuron, chlorthal, chlorthiamid, dimethyl disulfide, dimethyl phthalate, dimethylvinphos, chlorthiophos, chlortoluron, chloZolinate, chltosan, chole , dimexano, dimidazon, dimoxystrobin, dimpylate, calciferol, choline chloride, chromafenozide, cicloheximide, dimuron, dinex, dingjuneZuo, diniconazole, diniconazole cimectacarb, cimetacarb, cinerin I, cinerin II, cinerins, cini M. dinitramine, dinitrophenols, dinobuton, dinocap, don-ethyl, cinmethylin, cinosulfuron, cintofen, ciobutide, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, cisanilide, cismethrin, clacy fos, clefoxydim, clenpirin, clen dinoprop, dinosam, dinoseb, dinosulfon, , pyrin, clethodim, climbazole, cliodinate, clodinafop, cloeth dinoterb, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, ocarb, clofencet, clofenotane, clofentezine, clofenVinfos, , dioxation, diphacin, diphacinone, , clofibric acid, clofop, clomaZone, clomeprop, clonitralid, diphenamid, diphenamide, diphenyl Sulfone, diphenylam cloprop, cloproxydim, clopyralid, cloquintocet, cloransu ine, diphenylsulphide, diprogulic acid, dipropalin, dipropet lam, closantel, , clotrimazole, cloxyfonac, ryn, dipterex, dipyretitrone, dipyrithione, diduat, disodium cloxylacon, clozylacon, CMA, CMMP, CMP CMU, codle tetraborate, disoSultap, disparlure, disugran, disul, disul lure, collecalciferol, colophonate, copper 8-quinolinolate, firam, , ditalimfos, dithianon, dithicrofos, dithio copper acetate, copper acetoarsenite, copper arsenate, cop ether, dithiometon, dithiopyr, diuron, dixanthogen, d-limo per carbonate basic, copper hydroxide, copper naphthenate, nene, DMDS, DMPA, DNOC, dodemorph, dodicin, dodine, copper oleate, copper oxychloride, copper silicate, copper dofenapyn, doguadine, dominicalure, doramectin, DPC, dra Sulfate, copper Sulfate basic, copper Zinc chromate, cou Zoxolon, DSMA, d-trans-allethrin, d-trans-, dufu machlor, coumafene, coumafos, coumafuryl, , lin, dymron, EBEP, EBP. ebufos, ecdysterone, echlomeZol, , coumethoxystrobin, cournithoate, coumox EDB, EDC, EDDP edifenphos, eglinazine, emamectin, ystrobin, CPMC, CPMF, CPPC, credazine, cresol, cresylic EMPC, , enadenine, , endothal, acid, , , crotoxyfos, crotoxyphos, crufo endothall, , , enestroburin, enilconazole, mate, cryolite, cue-lure, cufraneb, cumyleron, cumyluron, enoxastrobin, ephirsulfonate, EPN, epocholeone, cuprobam, cuprous oxide, curcumenol, CVMP, cyanamide, epolfenonane, epoxiconazole, eprinomectin, epronaz, EPTC, cyanatryn, cyanazine, cyanofenphos, cyanogen, , erbon, , erluixiancaoan, esdepallethrine, cyanthoate, , cyanuric acid, cyaZofamid, , ESP, esprocarb, etacelasil, etaconazole, eta cybutryne, cyclafuramid, cyclanilide, cyclaniliprole, phos, etem, ethaboxam, ethachlor, ethalfluralin, ethametSul cyclethrin, cycloate, cyclohexiride, cycloprate, cyclopro furon, ethaprochlor, ethephon, ethidimuron, ethiofencarb, thrin, cyclopyrimorate, cyclosulfamuron, cycloxydim, ethiolate, , ethiozin, ethiprole, ethirimol, ethoate cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyflu methyl, ethobenzanid, ethofumesate, ethohexadiol, ethop thrin, cyhalofop, , cyhexatin, cymiazole, rop, , ethoxyfen, ethoxyquin, ethoxysulfuron, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyper ethychloZate, ethyl formate, ethyl pyrophosphate, ethylan, quat, , cyprazine, cyprazole, cyproconazole, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichlo cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyro ride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxy mazine, cythioate, cytrex, daimuron, dalapon, daminozide, propyl mercaptide, ethylmercury acetate, ethylmercury bro dayoutong, dazomet, DBCP, d-camphor, DCB, DCIP. mide, ethylmercury chloride, ethylmercury phosphate, DCPA, DCPTA, DCU, DDD, DDPP, DDT, DDVP, debac etinofen, ETM, etnipromid, etobenzanid, etofemprox, etox arb, decafentin, decamethrin, decarbofuran, deet, dehy azole, etridiazole, etrimfos, étrimphos, eugenol, EXD, droacetic acid, deiquat, delachlor, delnav, , famoxadone, famphur, fenac, fenamidone, fenaminosulf, , demephion-O, demephion-S, derneton, derine fenaminstrobin, , fenapanil, fenarimol, fenasu ton-methyl, demeton-O, demeton-O-methyl, demeton-S, lam, fenaZaflor, fenazaquin, fenbuconazole, fenbutatin demeton-S-methyl, demeton-S-methyl Sulphone, demeton oxide, fenchlorazole, fenchlorphos, fenclofos, fenclorim, S-methylsulphon, DEP depallethrine, derris, desmedipham, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenidin, desmetryn, desmetryne, d-fanshiluquebinguzhi, diafenthi fenitropan, , fenizon, fenjuntong, . uron, , dialifos, diallate, diamidafos, dianat, diato fenolovo, fenoprop, fenothiocarb, fenoxacrim, fenoxaniil, maceous earth, diatomite, , dibrom, dibutyl phtha fenoxaprop, fenoxaprop-P, fenoxasulfone, , fen late, dibutyl succinate, dicamba, dicapthon, dichlobenil. piclonil, fempirithrin, , fempropidin, fenpropi dichlofenthion, dichlofluanid, dichlone, dichloralurea, morph, fenpyraZamine, fenpyroximate, fenduinotrione, fen dichlorbenzuron, dichlorfenidirn, dichlorflurecol, dichlo ridazon, fenson, fensulfothion, fenteracol, fenthiaprop, rflurenol, dichlormate, dichlormid, dichloromethane, diclo , fenthion-ethyl, fentiaprop, fentin, fentraZamide, romeZotiaz, dichlorophen, dichlorprop, dichlorprop-P, fentrifanil, fenuron, fenuron-TCA, , ferbam, fer , dichlozolin, dichlozoline, diclobutrazol, diclo imzone, ferric phosphate, ferrous Sulfate, fipronil, flamprop, cymet, diclofop, diclalomeZine, dicloran, dicloSulam, dico flamprop-M, flaZaSulfuron, , flometoquin, floni fol, dicophane, dicoumrarol, dicresyl, , dicryl, camid, florasulam, fluacrypyrim, fluazifop, fluazifop-P, flu dicumarol, dicyclanil, dicyclonon, , dienochlor, aZinam, fluaZolate, fluaZuron, , flubenZimine, diethamquat, diethatyl, diethion, diethion, diethofencarb, flubrocythrinate, flucarbazone, flucetosulfuron, fluchloralin, dietholate, diethon, diethyl pyrocarbonate, diethyltolu flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluéné amide, , difenoconazole, difenopenten, difenox thyl, fluenetil, fluensulfone, flufenacet, flufenerim, flufeni uron, difenzoquat, , diflovidazin, , can, , flufenoxystrobin, flufenprox, flufenpyr. diflufenican, diflufenicanil, diflufenzopyr, diflumretorim, flufenzine, flufiprole, fluhexafon, , flumetover, dikegulac, dilor, dimatif, dimefluthrin, , dimefuron, flumetralin, flumetSulam, flumezin, flumiclorac, flumiox dimehypo, dirmepiperate, dirmetachlone, dimetan, direthac azin, flumipropyn, flunmorph, fluometuron, fluopicolide, arb, dirmethachlone, dimethachlor, dimethametryn, dimeth fluopyram, fluorbenside, fluoridamid, , fluo enamid, dimethenamid-P, dimethipin, dimethirimol, dime roacetic acid, fluorochloridone, fluorodifen, fluoroglycofen, US 2017/020880.6 A1 Jul. 27, 2017

fluoroimide, fluoromide, fluoromidine, fluoronitrofen, fluo rim, meperfluthrin, mephenate, mephosfolan, mepiduat, roxypyr, fluothiuron, fluotrimazole, fluoxastrobin, mepronil, meptyldinocap, mercaptodimethur, mercapto flupoxam, flupropacil, , flupropanate, flupyra phos, mercaptophos thiol, mercaptothion, mercuric chloride, difurone, flupyrsulfuron, fluguinconazole, , flura mercuric oxide, mercurous chloride, merphos, merphos Zole, flurecol, flurenol, fluridone, flurochloridone, fluromi oxide, mesoprazine, mesosulfuron, mesotrione, , dine, fluroxypyr, flurprimidol, flurSulamid, flurtamone, meSulfenfos, meSulphen, metacresol, , meta flusilazole, flusulfamide, flutenzine, fluthiacet, fluthiamide, laxyl, metalaxyl-M, metaldehyde, metam, metamifop, met flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, flux amitron, metaphos, metaxon, metaZachlor, metazosulfuron, ofenim, folpel, folpet, fomesafen, , foramsulfuron, metaZOXolon, metconazole, metepa, metflurazon, methaben forchlorfenuron, formaldehyde, , , ZthiaZuron, methacrifos, methalpropalin, metham, methami , fosamine, fosetyl, foSmethilan, fospirate, fos dophos, methasulfocarb, methazole, methfuroxam, methi thiazate, fosthietan, frontalin, fthalide, fuberidazole, fucao benzuron, , methiobencarb, , jing, fucaomi, fujunmanzhi, fullumi, fumarin, funaihecaol methiopyrisulfuron, methiotepa, methioZolin, methiuron, ing, fuphenthiourea, furalane, furalaxyl, furamethrin, methocrotophos, métholcarb, methometon, . furametpyr, furan , furathiocarb, furcarbanil, , methoprotryn, methoprotryne, methoduin-bu furconazole, furconazole-cis, furethrin, furfural, furilazole, tyl, methothrin, , methoxyfenozide, methoxy furmecyclox, furophanate, furyloxyfen, gamma-BHC, phenone, methyl apholate, methyl bromide, methyl eugenol, gamma-cyhalothrin, gamma-HCH, genit, gibberellic acid, methyl iodide, methyl isothiocyanate, methyl , gibberellin A3, gibberellins, gliftor, glitor, glucochloralose, methylacetophos, methylchloroform, methyldithiocarbamic glufosinate, glufosinate-P. glyodin, glyoxime, glyphosate, acid, methyldymron, methylene chloride, methyl-isofen glyphosine, gossyplure, grandlure, griseofulvin, guanoctine, phos, methylmercaptophos, methylmercaptophos oxide, guaZatine, halacrinate, halauXifen, halfenproX, halofenozide, methylmercaptophos thiol, methylmercury benzoate, meth halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop ylmercury dicyandiamide, methylmercury pentachlorophe P. haloxyfop-R, HCA, HCB, HCH, hemel, hempa, HEOD, noxide, methylneodecanamide, methylnitrophos, methyltri , heptafluthrin, heptenophos, heptopargil, her aZothion, metioZolin, metiram, metiram-zinc, bimycin, herbimycin A, heterophos, hexachlor, hexachloran, metobenzuron, metobromuron, , metolachlor, hexachloroacetone, hexachlorobenzene, hexachlorobutadi , metometuron, metominostrobin, metoSulam, ene, hexachlorophene, hexaconazole, hexaflumuron, metoxadiaZone, metoxuron, metrafenone, metriam, hexafluoramin, hexaflurate, hexalure, hexamide, hexazi metribuzin, , metriphonate, metSulfovax, metSul none, hexylthiofos, hexythiazox, HHDN, holosulf, homo furon, , mexacarbate, miechuwei, mieshuan, mie brassinolide, huancaiwo, huanchongjing, huangcaoling, wenjuzhi, milbemectin, , milineb, huanjunzuo, , hydrargaphen, hydrated lime, mima2nan, , MIPC, , MNAF, moguchun, hydrogen cyanamide, hydrogen cyanide, , molinate, moloSultap, momfluorothrin, monalide, moni hydroxyisoxazole, hymexazol, hyduincarb, IAA, IBA, IBP, Suron, monoamitraz, monochloroacetic acid, monocroto icaridin, imazalil, imazamethabenZ, imaZamox, imazapic, phos, monolinuron, monomehypo, monosulfiram, monosul imazapyr, imaZaquin, imazethapyr, imaZosulfuron, imiben furon, monosultap, monuron, monuron-TCA, morfamquat, conazole, imicyafos, , imidaclothiz, iminocta moroxydine, morphothion, morzid, moxidectin, MPMC, dine, , inabenfide, indanofan, indaziflam, indox MSMA, MTMC, muscalure, myclobutanil, myclozolin, acarb, inezin, infusorial earth, iodobonil, iodocarb, myricyl alcohol, N-(ethylmercury)-p-toluenesulphonanilide, iodofenphos, iodomethane, iodosulfuron, iofensulfuron, NAA, NAAm, nabam, naftalofos, , naphthalene, naph ioxynil, ipazine, IPC, ipconazole, ipfencarbazone, ipfentri thaleneacetamide, naphthalic anhydride, naphthalophos, fluconazole, iprobenfos, iprodione, iprovalicarb, iprymidam, naphthoxyacetic acids, naphthylacetic acids, naphthylin ipsdienol, ipsenol, IPSP, IPX, isamidofos, isazofos, isoben dane-1,3-diones, naphthyloxyacetic acids, naproanilide, Zan, isocarbamid, isocarbamide, isocarbophos, isocil, iso napropamide, napropamide-M, naptalam, natamycin, drin, isofenphos, isofenphos-methyl, isofetamid, isolan, NBPOS, neburea, neburon, nendrin, neonicotine, nichlorfos, isomethiozin, isonoruron, isopamphos, isopolinate, isopro niclofen, niclosamide, nicobifen, nicosulfuron, nicotine, carb, isoprocil, isopropalin, isopropaZol, isoprothiolane, iso nicotine sulfate, nifluridide, nikkomycins, NIP. nipyra proturon, isopyrazam, isopyrimol, isothioate, isotianil, clofen, nipyralofen, , , nitralin, nitrapy isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, rin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, isoxaflutole, isoxapyrifop, , isuron, , nitrothal-isopropyl. nobormide, nonanol, , norea, iXOXaben, izopamfos, izopamphos, japonilure, japothrins, norflurazon, nornicotine, noruron, novaluron, noviflumuron, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, NPA, nuarimol, nuranone, OCH, octachlorodipropyl ether, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, Jingan octhillinone, o-dichlorobenzene, ofurace, , o-phe mycin A, jodfenphos, juvenile hormone I, juvenile hormone nylphenol, orbencarb, orfralure, orthobencarb, ortho-dichlo II, juvenile hormone III, kadethrin, kappa-, kappa robenzene, orthosulfamuron, oryctalure, orysastrobin, , karbutilate, karetazan, kasugamycin, kejunlin, oryzalin, osthol, osthole, ostramone, ovatron, ovex, oxabe kelevan, ketospiradox, kieselguhr, kinetin, kinoprene, kiral trinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, . axyl, kresoxim-methyl, kuicaoxi, lactofen, lambda-cyhalo oxapyrazon, oxapyrazone, oxasulfuron, oxathiapiprolin, thrin, latilure, lead arsenate, lenacil, lepimectin, , oxaziclomefone, Oxine-copper, oxine-Cu, oxolinic acid, lianbenjingzhi, lime , , lineatin, linuron, lirim Oxpoconazole, oxycarboxin, Oxydemeton-methyl, fos, litlure, loopilure, , liXiancaolin, lvdingjunzhi, Oxydeprofos, oxydisulfoton, oxyenadenine, oxyfluorfen, lvfumijvzhi, lvXiancaolin, lythidathion, M-74, M-81, MAA, oxymatrine, oxytetracycline, oxythioquinox, PAC, magnesium phosphide, , maldison, maleic hydraz paclobutraZol, paichongding, palethrine, PAP. para-dichlo ide, malonoben, maltodextrin, MAMA, mancopper, manco robenzene, parafluron, paraquat, parathion, parathion Zeb, mandestrobin, mandipropamid, maneb, matrine, mazi methyl, parinol, , PCNB, PCP, PCP-Na, p-di dox, MCC, MCP, MCPA, MCPA-thioethyl, MCPB, MCPP. chlorobenzene, PDJ, pebulate, pédinex, pefurazoate, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, pelargonic acid, penconazole, pencycuron, pendimethalin, mecoprop-P, medimeform, medinoterb, medlure, mefenacet, penfenate, penflufen, penfluron, penoxalin, penoXSulam, mefenoxam, mefenpyr, mefluidide, megatomoic acid, melis pentachlorophenol, pentachlorophenyl laurate, pentano syl alcohol, melitoxin, MEMC, menazon, MEP mepanipy chlor, penthiopyriad, pentmethrin, pentoxaZone, perchlorde US 2017/020880.6 A1 Jul. 27, 2017 cone, perfluidone, , pethoxamid, PHC, phe simeton, simetryn, simetryne, Sintofen, S-kinoprene, slaked namacril, phenamacril-ethyl, phenaminosulf, phenazine lime, SMA, S-methoprene, S-metolachlor, sodium arsenite, oxide, phénétacarbe, phenisopham, phenkapton, phenmed Sodium azide, sodium chlorate, sodium cyanide, sodium ipham, phenmedipham-ethyl, phenobenzuron, phenothiol, fluoride, , sodium hexafluorosilicate, , phenproxide, , phenylmercuriurea, Sodium naphthenate, Sodium o-phenylphenoxide, Sodium phenylmercury acetate, phenylmercury chloride, phenyl orthophenylphenoxide, Sodium pentachlorophenate, Sodium mercury derivative of pyrocatechol, phenylmercury nitrate, pentachlorophenoxide, Sodium polysulfide, Sodium silico phenylmercury salicylate, , , , phosametine, phosaZetim, phosaZetin, phoscyclotin, phosdi fluoride, sodium tetrathiocarbonate, sodium thiocyanate, phen, phosethyl, , phosfolan-methyl, phosglycin, Solan, Sophamide, spinetoram, , spirodiclofen, , phosnichlor, phosphamide, , phos spiromesifen, spirotetramat, spiroxamine, stirofos, strepto phine, phosphinothricin, phosphocarb, phosphorus, phostin, mycin, , Sulcatol, Sulcofuron, Sulcotrione, Sulfal , phoxim-methyl, phthalide, phthalophos, late, SulfentraZone, Sulfiram, Sulfluramid, Sulfodiazole, Sul phthal thrin, picarbutraZOX, picaridin, picloram, picolinafen, fometuron, Sulfosate, Sulfo Sulfuron, Sulfotep, Sulfotepp, picoxystrobin, pimaricin, , pinoxaden, piperalin, , sulfoxide, sulfoxime, sulfur, sulfuric acid, sul piperazine, piperonyl butoxide, piperonyl cyclonene, pip furyl fluoride, Sulglycapin, Sulphosate, Sulprofos, Sultropen, erophos, piproctanly, piproctanyl, piprotal, pirimetaphos, swep, tau-fluvalinate, tavron, tazimcarb. TBTO, TBZ, TCA, , piriminil, pirimioxyphos, pirimiphos-ethyl, TCBA, TCMTB, TCNB, TDE, tebuconazole, tebufenozide, pirimiphos-methyl, pival, pivaldione, plifenate, PMA, PMP. , tebufloquin, , tebutam, tebuthi polybutenes, polycarbamate, polychlorcamphene, poly uron, tecloftalam, tecnaZene, tecoram, tedion, teflubenZuron, ethoxyquinoline, polyoxin D. polyoxins, polyoxorim, poly tefluthrin, tefuryltrione, tembotrione, , temephos, thialan, potassium arsenite, potassium azide, potassium tepa, TEPP, tepraloxydim, teproloxydim, terallethrin, terba cyanate, potassium ethylxanthate, potassium naphthenate, cil, terbucarb, terbuchlor, , terbumeton, terbuthyla potassium polysulfide, potassium thiocyanate, pp'-DDT. zine, terbutol, terbutryn, terbutryne, terraclor, terramicin, , precocene I, precocene II, precocene III, preti terramycin, tetcyclacis, tetrachloroethane, tetrachlorvin lachlor, primidophos, primisulfuron, probenazole, prochlo raz, proclonol, procyazine, procymidone, prodiamine, pro phos, tetraconazole, , tetradisul, tetrafluron, fenofos, profluazol, profluralin, profluthrin, profoxydim, , tetramethylfluthrin, tetramine, tetranactin, tet profurite-aminium, proglinazine, prohexadione, prohydro raniliprole, tetrapion, tetrasul, thallium Sulfate, thallous Sul jasmon, promacyl, promecarb, prometon, prometryn, prom fate, thenylchlor, theta-cypermethrin, thiabendazole, thia etryne, promurit, pronamide, propachlor, propafos, propami cloprid, thiadiazine, thiadifluor, , thiameturon, dine, propamocarb, propanil, propaphos, propaquizafop, thiapronil, thiazafluron, thiazfluron, thiazone, thiazopyr, thi propargite, proparthrin, propazine, propetamphos, propham, crofos, thicyofen, thidiazimin, thidiaZuron, thiencarbazone, propiconazole, propidine, propineb, propisochlor, , thifensulfuron, thifluzamide, thimerosal, thimet, thioben propoxycarbazone, propyl isome, propyrisulfuron, propyZ carb, thiocarboxime, thiochlorfenphim, thiochlorphen amide, produinazid, proSuler, prosulfalin, prosulfocarb, pro phime, thiocyanatodinitrobenzenes, thiocyclam, thiodan, Sulfuron, prothidathion, prothiocarb, prothioconazole, pro thiodiazole-copper, thiodicarb, thiofanocarb, , thiofos, , protrifenbute, proxan, prymidophos, thiofluoximate, thiohempa, thiomersal, thiometon, thion prynachlor, psoralen, psoralene, pydanon, pyflubumide, azin, thiophanate, thiophanate-ethyl, thiophanate-methyl, pymetrozine, pyracarbolid, pyracdofos, pyraclonil, pyra thiophos, thioquinox, thiosemicarbazide, thiosultap, thio clostrobin, pyraflufen, pyrafluprole, pyramat, pyrameto tepa, thioxamyl, , thiuram, thuringiensin, tiabenda strobin, pyraoxystrobin, pyrasulfotole, pyraziflumid, pyra Zole, tiadinil, tiafenacil, tiaojiean, TIBA, tifatol, tiocarbazil, Zolate, pyrazolynate, pyrazon, pyrazophos, pyrazosulfuron, tioclorim, tioxazafen, tioxymid, tirpate, TMTD, tolclofos pyrazothion, pyrazoxyfen, pyresmethrin, I, pyre methyl, tolfenpyrad, tolprocarb, tolpyralate, tolyfluanid, thrin II, , pyribambenz-isopropyl pyribambenz tolylfluanid, tolylmercury acetate, tomarin, toprameZone, propyl pyribencarb, pyribenZoxim, pyributicarb, pyriclor, , TPN, tralkoxydim, tralocythrin, , pyridaben, pyridafol, pyridalyl pyridaphenthion, pyrida tralopyril, , transpermethrin, tretamine, triacon phenthione, pyridate, pyridinitril, pyrifenox, pyrifluqui tanol, triadimefon, triadimenol, triafamone, triallate, tri nazon, pyriftalid, pyrimitaphos, pyrinethanil, pyrimicarbe, allate, triamiphos, triapenthenol, triarathene, triarimol, tria pyrimidifen, pyrininobac, pyriminostrobin, pyrimiphos Sulfuron, triazamate, triaZbutil, triaziflam, triaZophos, ethyl, pyrimriphos-rnthyl, pyrimisulfan, pyrimitate, pyrin triazothion, triaZoxide, tribasic copper chloride, tribasic cop uron, pyriofenone, , pyripropanol, , per sulfate, tribenuron, tribufos, tributyltin oxide, tricamba, pyrisoxazole, pyrithiobac, pyrolan, pyroquilon, pyroxasul trichlamide, trichlopyr, trichlorfon, trichlorimetaphos-3, fone, pyroxSulam, pyroxychlor, pyroxyfur, qincao Suan, trichloronat, , trichlorotrinitrobenzenes, trichlo qingkuling, quassia, quinacetol, , quinalphos rphon, triclopyr, triclopyricarb, tricresol, tricyclazole, tricy methyl, quinaZamid, quinclorac, quinconazole, quinmerac, clohexyltin hydroxide, tridemorph, tridiphane, trietazine, quinoclamine, quinomethionate, quinonamid, quinothion, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, tri quinoxyfen, quintiofos, quintoZene, quizalofop, quizalofop fludirnmoxazin, triflumeZopyrim, triflumizole, triflumuron, P. quwenzhi, quyingding, rabenzazole, rafoxanide, R-dini tarifurausulfuronn, triflusulfuron, trifop, trifopsime, trifo conazole, rebemide, reglone, renriduron, rescalure, res rine, trihydroxytriazine, trimedlure, trimethacarb, methrin, rhodethanil, rhodojaponin-III, ribavirin, trimeturon, trinexapac, triphenyltin, triprene, tripropindan, rinsulfuron, rizazole, R-metalaxyl, rodethanil, ronnel, rote triptolide, tritac, trithialan, triticonazole, tritosulfuron, trunc none, ryania, Sabadilla, saflufenacil, saijunmao, Saisentong, call, tuoyelin, uniconazole, uniconazole-P. urbacide, ure salicylanilide, Salifluofen, Sanguinarine, Santonin, S-bioal depa, Valerate, validamycin, validamycin A, Valifenalate, lethrin, , , Sebuthylazine, secbumeton, valone, Varnidothion, Vangard, Vaniliprole, Vernolate, Vin sedaxane, Selarectin, semiamitraz, , Sesamolin, ses cloZolin, vitamin D3, , Xiaochongliulin, Xinjunan, one, Sethoxydim, Sevin, Shuangjiaancaolin, Shuangjianan Xiwojunan, Xiwojunzhi. XMC, Xylachlor, Xylenols, Xylyl caolin, S-hydroprene, Siduron, sifumijVZhi, siglure, Silaflu carb, Xymiazole, yishijing, Zarilamid, Zeatin, Zengxiaoan, ofen, silatrane, silica aerogel, silica gel, silthiofam, Zengxiaolin, Zeta-cypermethrin, Zinc naphthenate, Zinc silthiopham, silthiophan, silveX, Simazine, Simeconazole, phosphide, Zinc thiazole, Zinc thioZole, Zinc trichlorophen US 2017/020880.6 A1 Jul. 27, 2017 6 ate, Zinc trichlorophenoxide, Zineb, Ziram, Zolaprofos, Zoo- N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N- , Zoxamide, Zuoanjunzhi, Zuocaoan, Zuojunzhi, ethyl-3-((3,3,3-trifluoropropyl)thio)propanamide Zuomihuanglong, C-chlorohydrin, C-ecdysone, C-mul- 0024. In this document, this molecule, for ease of use, is tistriatin, C.-naphthaleneacetic acids, and B-ecdysone; named as 'AI-1: 0023 (2) the following molecule 0025 (3) a molecule known as which has the following structure

and 0026 (4) the following molecules in Table A TABLE A

Structure of M - active ingredients

Name Structure

M1 R

s -Nn CH r e! I N N R = CH, N R = H, Me

M2 X 21

N N

X = F, Cl R = H, F

M3 Br N -o HC1 N H N N M N C O C C % \ US 2017/020880.6 A1 Jul. 27, 2017

TABLE A-continued

Structure of M - active ingredients

Name Structure

0027 As used in this disclosure, each of the above is an 0034. The term “aryl' means a cyclic, aromatic substitu active ingredient, and two or more are active ingredients. ent consisting of hydrogen and carbon, for example, phenyl, For more information consult the "COMPENDIUM OF PESTICIDE naphthyl, and biphenyl. COMMON NAMEs' located at Alanwood.net and various edi 0035. The term “biopesticide” means a microbial biologi tions, including the on-line edition, of “THE PESTICIDE cal pest control agent which, in general, is applied in a MANUAL located at bcpcdata.com. similar manner to chemical pesticides. Commonly they are 0028. The term “alkenyl means an acyclic, unsaturated bacterial, but there are also examples of fungal control (at least one carbon-carbon double bond), branched or agents, including Trichoderma spp. and Ampelomyces unbranched, Substituent consisting of carbon and hydrogen, quisqualis. One well-known example is Bacil for example, vinyl, allyl, butenyl, pentenyl, and hexenyl. lus thuringiensis, a bacterial disease of , Cole 0029. The term “alkenyloxy' means an alkenyl further optera, and Diptera. include products based consisting of a carbon-oxygen single bond, for example, O allyloxy, butenyloxy, pentenyloxy, hexenyloxy. 0036 (1) entomopathogenic fungi (e.g. Metarhizium 0030 The term “alkoxy' means an alkyl further consist anisopliae): ing of a carbon-oxygen single bond, for example, methoxy, 0037 (2) entomopathogenic nematodes (e.g. Stein ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert ernema feltiae); and butoxy. 0038 (3) entomopathogenic viruses (e.g. pomo 0031. The term “alkyl means an acyclic, saturated, nella granulovirus). branched or unbranched, Substituent consisting of carbon 0039. Other examples of entomopathogenic organisms and hydrogen, for example, methyl, ethyl, propyl, isopropyl. include, but are not limited to, baculoviruses, protozoa, and butyl, and tert-butyl. Microsporidia. For the avoidance of doubt biopesticides are 0032. The term “alkynyl' means an acyclic, unsaturated considered to be active ingredients. (at least one carbon-carbon triple bond), branched or 0040. The term “cycloalkenyl' means a monocyclic or unbranched, Substituent consisting of carbon and hydrogen, polycyclic, unsaturated (at least one carbon-carbon double for example, ethynyl, propargyl, butynyl, and pentynyl. bond) Substituent consisting of carbon and hydrogen, for 0033. The term “alkynyloxy' means an alkynyl further example, cyclobutenyl, cyclopentenyl, cyclohexenyl, nor consisting of a carbon-oxygen single bond, for example, bornenyl, bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexa pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy. hydronaphthyl, and octahydronaphthyl. US 2017/020880.6 A1 Jul. 27, 2017

0041. The term “cycloalkenyloxy' means a cycloalkenyl domesticated are residing; the interior or exterior further consisting of a carbon-oxygen single bond, for Surfaces of buildings (such as places where grains are example, cyclobutenyloxy, cyclopentenyloxy, norbornemy stored); the materials of construction used in buildings (such loxy, and bicyclo2.2.2]octenyloxy. as impregnated wood); and the soil around buildings. 0042. The term “cycloalkyl means a monocyclic or 0053. The phrase “MoA Material” means a material polycyclic, Saturated Substituent consisting of carbon and having a mode of action (“MoA) as indicated in IRAC hydrogen, for example, cyclopropyl, cyclobutyl, cyclopen MoA Classification v. 7.3, located at irac-online.org., which tyl, norbornyl, bicyclo2.2.2]octyl, and decahydronaphthyl. describes: 0043. The term “cycloalkoxy' means a cycloalkyl further 0054 (1) Acetylcholinesterase (AChE) inhibitors; consisting of a carbon-oxygen single bond, for example, 0055 (2) GABA-gated chloride channel antagonists; cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norborny 0056 (3) Sodium channel modulators; loxy, and bicyclo2.2.2]octyloxy. 0057 (4) Nicotinic acetylcholine receptor (nAChR) ago 0044. The term “halo' means fluoro, chloro, bromo, and nists; iodo. 0058 (5) Nicotinic acetylcholine receptor (nAChR) 0045. The term “haloalkoxy' means an alkoxy further allosteric activators; consisting of from one to the maximum possible number of 0059 (6) Chloride channel activators: identical or different, halos, for example, fluoromethoxy, 0060 (7) Juvenile hormone mimics; trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, 0061 (8) Miscellaneous nonspecific (multi-site) inhibi trichloromethoxy, 1.1.2.2-tetrafluoroethoxy, and pentafluo tors; roethoxy. 0062 (9) Modulators of Chordotonal Organs; 0046. The term “haloalkyl means an alkyl further con 0063 (10) growth inhibitors: sisting of from one to the maximum possible number of 0064 (11) Microbial disruptors of insect midgut mem identical or different, halos, for example, fluoromethyl, branes; trifluoromethyl, 2,2-difluoropropyl, chloromethyl, trichlo 0065 (12) Inhibitors of mitochondrial ATP synthase: romethyl, and 1,1,2,2-tetrafluoroethyl. 0.066 (13) Uncouplers of oxidative phosphorylation via 0047. The term "heterocyclyl means a cyclic substituent disruption of the proton gradient; that may be aromatic, fully saturated, or partially or fully 0067 (14) Nicotinic acetylcholine receptor (nAChR) unsaturated, where the cyclic structure contains at least one channel blockers; carbon and at least one heteroatom, where said heteroatom 0068 (15) Inhibitors of chitin biosynthesis, type 0: is nitrogen, Sulfur, or oxygen. Examples are: 0069 (16) Inhibitors of chitin biosynthesis, type 1: 0048 (1) aromatic heterocyclyl substituents include, but (0070 (17) Moulting disruptor, Dipteran; are not limited to, benzofuranyl, benzoisothiazolyl, benzo 0071 (18) Ecdysone receptor agonists; isoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl cin 0072 (19) Octopamine receptor agonists; nolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, 0073 (20) Mitochondrial complex III electron transport isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazoli nyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyra inhibitors; Zolyl pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazoli 0074 (21) Mitochondrial complex I electron transport nyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, inhibitors; thiazolyl, thienyl, triazinyl, and triazolyl; 0075 (22) Voltage-dependent sodium channel blockers; 0049 (2) fully saturated heterocyclyl substituents (0076 (23) Inhibitors of acetyl CoA carboxylase; include, but are not limited to, piperazinyl, piperidinyl, 0077 (24) Mitochondrial complex IV electron transport morpholinyl, pyrrolidinyl, tetrahydrofuranyl, and tetrahy inhibitors; dropyranyl: 0078 (25) Mitochondrial complex II electron transport 0050 (3) partially or fully unsaturated heterocyclyl sub inhibitors; and stituents include, but are not limited to, 1,2,3,4-tetrahydro 0079 (28) receptor modulators. quinolinyl, 4.5-dihydro-oxazolyl. 4.5-dihydro-1H-pyra 0080. The phrase “MoA material group alpha' (hereafter Zolyl. 4,5-dihydro-isoxazolyl, and 2,3-dihydro-1,3,4- “MoAMGA) means collectively the following materials, oxadiazolyl; and abamectin, acephate, acequinocyl, , acrinathrin, 0051 (4) Additional examples of heterocyclyls include alanycarb, aldicarb, allethrin, alpha-cypermethrin, alu the following: minium phosphide, amitraz, azamethiphos, azinphos-ethyl, azinphos-methyl, azocyclotin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, , bioallethrin S-cyclopentenyl isomer, biores methrin, bistrifluron, borax, buprofezin, butocarboxim, butoxycarboxim, cadusafos, , carbaryl, | carbofuran, carbosulfan, cartap hydrochloride, chlorantra O niliprole, chlordane, chlorethoxyfos, , chlorfen thietanyl thietanyl-oxide and thietanyl-dioxide. Vinphos, chlorfluaZuron, chlormephos, chloropicrin, chlo rpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezine, clothianidin, coumaphos, cyanide, cyanophos, 0052. The term “locus’ means a habitat, breeding ground, cyantraniliprole, cycloprothrin, cyenopyrafen, cyflu plant, seed, soil, material, or environment, in which a pest is metofen, cyfluthrin, cyhalothrin, cyhexatin, cypermethrin, growing, may grow, or may traverse, for example, a locus cyphenothrin, , d-cis-trans-allethrin, DDT, del may be: where crops, trees, fruits, cereals, fodder species, tamethrin, demeton-S-methyl, diafenthiuron, diazinon, vines, turf, and/or ornamental plants are growing; where dichlorvos/DDVP. dicrotophos, diflovidazin, diflubenzuron, US 2017/020880.6 A1 Jul. 27, 2017 , dimethylvinphos, dinotefuran, disulfoton, spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclo DNOC, d-trans-allethrin, emamectin benzoate, empenthrin, Cephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus endosulfan, EPN, esfenvalerate, ethiofencarb, ethion, ethop spp., Ips spp., Lyctus spp., Megascelis spp., Melligethes spp., rophos, , etoxazole, famphur, fenamiphos, Otiorhynchus spp., Otiorhynchus spp., Pantomorus spp., fenaZaquin, fenbutatin oxide, fenitrothion, fenobucarb, Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., fenoxycarb, fenpropathrin, fenpyroximate, fenthion, fenva Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphe lerate, flonicamid, fluacrypyrim, flubendiamide, flucyclox nophorus spp., Sitophilus spp., and Tribolium spp. A non uron, flucythrinate, flufenoxuron, flumethrin, flupyradifu exhaustive list of particular species includes, but is not rone, formetanate, fosthiazate, furathiocarb, gamma limited to, Acanthoscelides Obtectus, Agrilus planipennis, cyhalothrin, halfenproX, halofenozide, heptenophos, Anoplophora glabripennis, Anthonomus grandis, Ataenius hexaflumuron, hexythiazox, hydramethylnon, hydroprene, spretulus, Atomaria linearis, Bothynoderes punctiventris, imicyafos, imidacloprid, imiprothrin, , isofen Bruchus pisorum, Callosobruchus maculatus, Carpophilus phos, isoprocarb, isoxathion, kadethrin, kinoprene, lambda hemipterus, vittata, Cerotoma trifurcata, Ceuto cyhalothrin, lepimectin, lufenuron, malathion, mecarbam, rhynchus assimilis, Ceutorhynchus mapi, Conoderus sca metaflumizone, , methidathion, methiocarb, laris, Conoderus stigmosus, Conotrachelus menuphar, Coti methomyl, methoprene, (methoxyaminothio-phosphoryl) nis initida, Crioceris asparagi, ferrugineus, salicylate, methoxychlor, methoxyfenozide, methyl bro Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocoptu mide, metolcarb, mevinphos, milbemectin, , rus adspersus, Deporaus marginiatus, Dermestetes lard naled, nicotine, nitenpyram, novaluron, noviflumuron, arius, Dermestes maculatus, Epillachna varivestis, Fausti oxamyl, oxydemeton-methyl, parathion, parathion-methyl, nus cubae, Hylobius pales, Hypera postica, Hypothenemus permethrin, phenothrin, phenthoate, phorate, phosalone, hampei, Lasioderma serricorne, Leptinotarsa decemlineata, phosmet, phosphamidon, phosphine, phoxim, pirimicarb, Liogeny's fuscus, Liogenys suturalis, Lissorhoptrus Oryzo pirimiphos-methyl, prallethrin, , propargite, pro philus, Maecolaspis joliveti, Melanotus communis, petamphos, propoXur, prothiofos, pymetrozine, pyraclofos, Melligethes aeneus, Melolontha melolontha, brevis, pyrethrin, pyridaben, pyridaphenthion, pyrimidifen, Oberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, pyriproxyfen, quinalphos, resmethrin, rotenone, , Oryzaephilus surinamensis, Oulema melanopus, Oulema spinetoram, spinosad, Spirodiclofen, spiromesifen, spirote Oryzae, Phylophaga cuyabana, Popillia japonica, Pros tramat, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, tephanus truncatus, Rhyzopertha dominica, Sitona lineatus, tartar emetic, tau-fluvalinate, tebufenozide, tebufenpyrad, Sitophilus granarius, Sitophilus Oryzae, Sitophilus zeanais, tebupirimfos, teflubenzuron, tefluthrin, temephos, terbufos. Stegobium paniceum, Tribolium castaneum, Tribolium con , tetradifon, tetramethrin, tetramethrin, filsum, Trogoderma variabile, and tenebrioides. theta-cypermethrin, , thiamethoxam, thiocyclam, I0086 (5) Order Dermaptera. A non-exhaustive list of thiodicarb, thiofanox, thiometon, thiosultap-sodium, tolfen particular species includes, but is not limited to, Forficula pyrad, tralomethrin, transfluthrin, triaZamate, triaZophos, auricularia. trichlorfon, triflumuron, trimethacarb, vamidothion, XMC, I0087 (6) Order Blattaria. A non-exhaustive list of par Xylylcarb, Zeta-cypermethrin, and . For the ticular species includes, but is not limited to, Blattella avoidance of doubt, each of the foregoing materials is an germanica, Blatta Orientalis, Parcoblatta pennsylvanica, active ingredient. Periplaneta americana, Periplaneta australasiae, Periplan 0081. The term "pest” means an organism that is detri eta brunnea, Periplaneta fuliginosa, Pycnoscelus surina mental to humans, or human concerns (such as, crops, food, mensis, and Supella longipalpa. livestock, etc.), where said organism is from Phyla Arthro I0088 (7) Order Diptera. A non-exhaustive list of particu poda, Mollusca, or Nematoda, particular examples are , lar genera includes, but is not limited to, Aedes spp., aphids, , bristletails, cockroaches, crickets, earwigs, Agromyza spp., Anastrepha spp., Anopheles spp., Bactro , , grasshoppers, leafhoppers, lice (including sea cera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., lice), locusts, , , nematodes, scales, Symphylans, Contarinia spp., Culex spp., Dasineura spp., Delia spp., termites, thrips, , wasps, and whiteflies, additional Drosophila spp., spp., Fannia spp., Hvlemyia spp., Liri examples are pests in: omyza spp., Musca spp., Phorbia spp., Tabanus spp., and 0082 (1) Subphyla , Myriapoda, Crustacea, Tipula spp. A non-exhaustive list of particular species and ; includes, but is not limited to, Agromyza frontella, Anas 0083 (2) Classes of Arachnida, Maxillopoda, Symphyla, trepha suspensa, Anastrepha ludens, Anastrepha Obliga, and Insecta; Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera 0084 (3) Order Anoplura. A non-exhaustive list of par invadens, Bactrocera Zonata, Ceratitis capitata, Dasineura ticular genera includes, but is not limited to, Haematopinus brassicae, Delia platura, Fannia canicularis, Fannia sca spp., Hoplopleura spp., Linognathus spp., Pediculus spp., laris, Gasterophilus intestinalis, Gracilia perseae, Haema and Polyplax spp. A non-exhaustive list of particular species tobia irritans, Hypoderma lineatum, Liriomyza brassicae, includes, but is not limited to, Haematopinus asini, Hae Melophagus Ovinus, Musca autumnalis, Musca domestica, matopinus Suis, Linognathus setosus, Linognathus Ovillus, Oestrus ovis, Oscinella frit, betae, Psila rosae, Pediculus humanus capitis, Pediculus humanus humanus, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis men and Pthirus pubis. dax, Sitodiplosis mosellana, and Stomoxys calcitrans. 0085 (4) Order Coleoptera. A non-exhaustive list of I0089 (8) Order . A non-exhaustive list of par particular genera includes, but is not limited to, Acanthos ticular genera includes, but is not limited to, Adelges spp., Celides spp., Agriotes spp., Anthonomus spp., Apion spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema Coccus spp., Empoasca spp., Lepidosaphes spp., Lagyno US 2017/020880.6 A1 Jul. 27, 2017 tomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., tilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Cram Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus bus spp., Diaphania spp., Diatraea spp., Earias spp., Ephes spp., Planococcus spp., Pseudococcus spp., Rhopalosiphum tia spp., Epimecis spp., Feltia spp., Gortyna spp., spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocol Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unas letis spp., Loxagrotis spp., Malacosoma spp., Peridroma pis spp. A non-exhaustive list of particular species includes, spp., spp., Pseudaletia spp., Sesamia spp., but is not limited to, Acrosternum hilare, Acyrthosiphon Spodoptera spp., Synanthedon spp., and Yponomeuta spp. A pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleuro non-exhaustive list of particular species includes, but is not thrixus floccosus, Amrrasca biguttula biguttula, Aonidiella limited to, Achaea janata, Adoxophyes Orana, Agrotis ipsi aurantil, Aphis gossypii, Aphis glycines, Aphis pomi, Aula lon, Alabama argillacea, Amorbia cuneana, Amyelois tran corthum Solani, Bemisia argentifolii, Bemisia tabaci, Blissus sitella, defectaria, Anarsia lineatella, Ano leucopterus, Brachycorynella asparagi, Brevennia rehi, mis Sabulifera, Anticarsia gemmatalis, Archips argyrospilla, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes Archips rosana, Argyrotaenia citrana, Autographa gamma, rubens, Cimex hemipterus, Cimex lectularius, Dagbertus Bonagota Cranaodes, cinnara, Bucculatrix thurberi fasciatus, Dichelops fircatus, Diuraphis noxia, Diaphorina ella, Capua reticulana, Carposina niponensis, Chlumetia citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa trans versa, Choristoneura rosaceana, Cnaphalocrocis meditabunda, Eriosoma lanigerum, maura, medinalis, Conopomorpha cramerella, Cossus cossus, Euschistus heros, Euschistus servus, Helopeltis antonii, Cydia caryana, Cydia funebrana, Cydia molest, Cydia nigri Helopeltis theivora, Icerya purchasi, Idioscopus initidulus, cana, Cydia nigricana, Cydia pomonella, Darna diducta, Laodelphax striatellus, Leptocorisa Oratorius, Leptocorisa Diatraea saccharalis, Diatraea grandiosella, Earias insu varicornis, Lygus hesperus, Maconellicoccus hirsutus, Mac lana, Earias vittella, Ecdytolopha aurantianum, Elasmopal rosiphum euphorbae, Macrosiphumrin granarium, Macros pus lignosellus, Ephestia cautella, Ephestia elutella, Ephes phumrin rosae, Macrosteles quadrilineatus, Mahanarva tia kuehniella, Epinotia aporema, Epiphyas postvittana, fimbiolata, Metopolophium dirhodium, Mictis longicornis, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Myzus persicae, Nephotettix cinctipes, Neurocolpus longi Grapholita molesta, Hedylepta indicata, Helicoverpa rostris, Nezara viridula, Nilaparvata lugens, Parlatoria armigera, Helicoverpa zea, Heliothis virescens, Hellula pergandii, Parlatoria Ziziphi, Peregrinus maidis, Phylloxera undalis, Keiferia lycopersicella, Leucinodes Orbonalis, Leu vitifoliae, Physokermes piceae, Phytocoris Californicus, coptera coffeella, malifoliella, Lobesia botrana, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus LOxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, lineatus, Psallus vaccinicola, Pseudacy.sta perseae, Pseudo Mahasena corbetti, Mamestra brassicae, Maruca testulalis, coccus brevipes, Ouadraspidiotus perniciosus, Rhopalosi Metisa plana, Mythinna unipruncta, Neoleucinodes elegan phumrin maidis, Rhopalosiphum padi, Saissetia oleae, Scap talis, Nymphula depunctalis, Operophtera brumata, tocoris Castanea, Schizaphis graminum, Sitobion avenae, Ostrinia nubilalis, vesulia, Pandemis cerasana, Sogatella furcifera, Trialeurodes vaporariorum, Trialeu Pandemis heparana, Papilio demodocus, Pectinophora gos rodes abutiloneus, Unaspis yanonensis, and Zulia entrerri sypiella, Peridroma Saucia, Perileucoptera coffeella, Phtl CF2C horinaea operculella, Phyllocnistis citrella, Pieris rapae, 0090 (9) Order Hymenoptera. A non-exhaustive list of Plathy pena scabra, Plodia interpunctella, Plutella xylos particular genera includes, but is not limited to, Acromyrmex tella, Polychrosis viteana, endocarpa, Prays oleae, spp., Atta spp., Camponotus spp., Diprion spp., Formica Pseudaletia unipuncta, Pseudoplusia includens, Rachiplu spp., Monomorium spp., Neodiprion spp., Pogonomyrmex sia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia spp., Polistes spp., Solenopsis spp., Vespula spp., and Xvlo nonagrioides, Setora initens, Sitotroga cerealella, Spargan copa spp. A non-exhaustive list of particular species othis pilleriana, Spodoptera exigua, Spodoptera frugiperda, includes, but is not limited to, Athalia rosae, Atta texana, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Iridomyrmex humilis, Monomorium minimum, Monomo Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera rium pharaonis, Solenopsis invicta, Solenopsis geminata, pyrina, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, 0093 (12) Order Mallophaga. A non-exhaustive list of and Tapinoma sessile. particular genera includes, but is not limited to, Anaticola 0091 (10) Order Isoptera. A non-exhaustive list of par spp., Bovicola spp., Chelopistes spp., Goniodes spp., Mena ticular genera includes, but is not limited to, canthus spp., and Trichodectes spp. A non-exhaustive list of spp., Cornitermes spp., Cryptotermes spp., Heterotermes particular species includes, but is not limited to, Bovicola spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., bovis, Bovicola caprae, Bovicola ovis, Chelopistes melea Marginitermes spp., Microcerotermes spp., Procorinitermes gridis, Goniodes dissimilis, Goniodes gigas, Menacanthus spp., Reticulitermes spp., Schedorhinotermes spp., and Zoo stramineus, Menopon gallinae, and Trichodectes canis. termopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, (0094) (13) Order . A non-exhaustive list of Coptotermes frenchi, Coptotermes formosanus, Hetero particular genera includes, but is not limited to, Melanoplus termes aureus, Microtermes Obesi, Reticulitermes banyule spp., and Pterophylla spp. A non-exhaustive list of particular insis, Reticulitermes grassei, Reticulitermes flavipes, Reticu species includes, but is not limited to, Anabrus simplex, litermes hageni, Reticulitermes hesperus, Reticulitermes Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa Santonensis, Reticulitermes speratus, Reticulitermes tibialis, brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, and Reticulitermes virginicus. retinerve, Schistocerca gregaria, and Scud 0092 (11) Order Lepidoptera. A non-exhaustive list of deria furcata. particular genera includes, but is not limited to, Adoxophyes 0.095 (14) Order Siphonaptera. A non-exhaustive list of spp., Agrotis spp., Argyrotaenia spp., CaCOecia spp., Calop particular species includes, but is not limited to, Cerato US 2017/020880.6 A1 Jul. 27, 2017 11 phyllus gallinae, niger; Ctenocephalides per hectare to about 500 grams per hectare, and it is even canis, Cocephalides Canis, Ctenocephalides felis, and Pulex more preferably from about 0.0001 grams per hectare to irritans. about 50 grams per hectare. 0096 (15) Order Siphonostomatoida. A non-exhaustive list of particular species includes, but is not limited to, Lepeophtheirus salmonis, Lepeophtheirus pectoralis, Cali DETAILED DESCRIPTION OF THE gus elongatus, and Caligus Clemensi. DISCLOSURE 0097 (16) Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Calliothrips (0103) This document discloses molecules of Formula spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A One non-exhaustive list of particular species includes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella Schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips Orientalis, Formula One and Thrips tabaci. 0098 (17) Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Thermobia spp. 0099 (18) Order Acarina. A non-exhaustive list of par ticular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Olig Onychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus Siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus Schlechtendali, Amblyomma americanum, Brevipal pus obovatus, Brevipalpus phoenicis, Dermacentor variabi wherein: lis, Dermatophagoides pteronyssinus, Eotetranychus car 0104 (A) R', R. R. R', R', and R' are each inde pini, Notoedres cati, Oligonychus coffeae, Oligonychus pendently selected from the group consisting of H. F. Cl, Br, ilicis, Panonychus citri, Panonychus ulmi, Phylocoptruta I, CN, (C-C)alkyl, (C-C)haloalkyl, (C-C)alkoxy, and oleivora, Polyphagotarisonemus latus, Rhipicephalus San (C-C)haloalkoxy: guineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tet ranychus urticae, and Varroa destructor: 0105 (B) R. R. and Rare each independently selected 0100 (19) Order Symphyla. A non-exhaustive list of from the group consisting of H, F, Cl, Br, I, CN, (C-C) particular species includes, but is not limited to, Scutigerella alkyl, (C-C)alkenyl, (C-C)alkynyl, (C-C)haloalkyl, immaculata. (C-C)alkoxy, and (C-C)haloalkoxy; 0101 (20) Phylum Nematoda. A non-exhaustive list of 0106 (C) R' is (C-C)haloalkyl: particular genera includes, but is not limited to, Aph elen.choides spp., Belonolaimus spp., Criconemella spp., I0107 (D) R is selected from the group consisting of (F), Dity lenchus spp., Heterodera spp., Hirschmanniella spp., H, F, Cl, Br, I, CN, (C-C)alkyl, (C-C)haloalkyl, (C-C) Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and alkoxy, and (C-C)haloalkoxy; Radopholus spp. A non-exhaustive list of particular sp. I0108 (E) R' is selected from the group consisting of (F), includes, but is not limited to, Dirofilaria immitis, Het erodera zeae, Meloidogyne incognita, Meloidogyne F. Cl, Br, I, CN, (C-C)alkyl, (C-C)alkenyl, (C-C) javanica, Onchocerca volvulus, Radopholus similis, and alkynyl, (C-C)haloalkyl, (C-C)alkoxy, and (C-C)ha Rotylenchulus reniformis. loalkoxy; 0102 The phrase “pesticidally effective amount’ means 0109 (F) Rand R' together can optionally form a 3- to the amount of a pesticide needed to achieve an observable 5-membered saturated or unsaturated, hydrocarbyl link, effect on a pest, for example, the effects of necrosis, death, retardation, prevention, removal, destruction, or otherwise 0110 wherein said hydrocarbyl link may optionally be diminishing the occurrence and/or activity of a pest in a substituted with one or more substituents independently locus, this effect may come about when, pest populations are selected from the group consisting of F, Cl, Br, I, and CN: repulsed from a locus, pests are incapacitated in, or around, 0111 (G) Q is selected from the group consisting of O or a locus, and/or pests are exterminated in, or around, a locus. S; Of course, a combination of these effects can occur. Gen erally, pest populations, activity, or both are desirably 0112 (H) L is (C-C)alkyl: reduced more than fifty percent, preferably more than 90 percent, and most preferably more than 99 percent. In 0113 (I) n is 0, 1, or 2: general a pesticidally effective amount, for agricultural I0114 (J) R'' is selected from the group consisting of purposes, is from about 0.0001 grams per hectare to about (C-C)alkyl, (C-C)alkenyl, (C-C)cycloalkyl, (C-C) 5000 grams per hectare, preferably from about 0.0001 grams haloalkyl, (C-C)alkoxy, (C-C)haloalkoxy, and phenyl, US 2017/020880.6 A1 Jul. 27, 2017

0115 wherein each alkyl, alkenyl, cycloalkyl, haloalkyl, 0129. In another embodiment: alkoxy, haloalkoxy, and phenyl may optionally be substi tuted with one or more substituents independently selected 0130 (A) R', R, R, R'', R', and R' are H: from the group consisting of F, Cl, Br, I, CN, and OH; and I0131 (B) R, R, and Rare each independently selected from the group consisting of H. F. Cl, Br, (C-C)alkyl, and 0116 agriculturally acceptable acid addition salts, salt (C-C)alkenyl: derivatives, Solvates, ester derivatives, crystal polymorphs, isotopes, resolved Stereoisomers, and tautomers, of the mol (0132) (C) R' is (C-C)haloalkyl: ecules of Formula One. 0.133 (D) R is H: 0117. In another embodiment R', R,R,R,R,R,R'', R', and R' are H. This embodiment may be used in I0134 (E) R' is selected from the group consisting of C1, combination with the other embodiments of R. R. R', Q, Br, (C-C)alkyl, and (C-C)haloalkyl; L., n, and R''. 0.135 (G) Q is O: 0118. In another embodiment R is C1, Br, or CH. This 0.136 (H) L is (C-C)alkyl; embodiment may be used in combination with the other embodiments of R. R. R. R. R. R. R. R. R. R'', I0137 (I) n is 0, 1, or 2: Q, R, L, n, and R''. I0138 (J) R' is selected from the group consisting of (C-C)alkyl and (C-C)haloalkyl, 0119). In another embodiment R is F, Cl, Br, or CH=CH2. This embodiment may be used in combination 0.139 wherein each alkyl or haloalkyl may optionally be with the other embodiments of R', R. R. R. R. R. R. substituted with one or more substituents independently R0, R, R2, Q, R, L, n, and R. selected from the group consisting of F, Cl, Br, I, CN, and 0120. In another embodiment R is C1, Br, or CH. This OH. embodiment may be used in combination with the other embodiments of R', R. R. R. R. R. R. R', R'', R', Preparation of Benzyl Halides Q, R, L, n, and R''. 0140 Benzyl alcohol 1-3, wherein R. R. R. R. R. R. 0121. In another embodiment R. R. and Rare C1. This and R are as previously disclosed, may be prepared in embodiment may be used in combination with the other several ways. Ketones 1-1 may be prepared by treating embodiments of R', R. R. R. R. R. R'', R', Q, R', bromobenzenes with a lithium base such as n-butyllithium in L, n, and R''. a polar aprotic solvent preferably diethyl ether at tempera tures from about -78° C. to about 0° C. followed by 0122) In another embodiment R7 is (C-C)haloalkyl. treatment with esters RC(O)O(C-C)alkyl, wherein R is This embodiment may be used in combination with the other as previously disclosed, such as ethyl 2,2-difluoropropano embodiments of R', R. R. R. R. R. R. R. R'', R', ate (not shown). Treatment of ketones 1-1, wherein R', R, Q, R, L, n, and R''. R. R. R. and R7 are as previously disclosed, with a (0123. In another embodiment R7 is CF, or CFCH. This reducing agent such as Sodium borohydride, in the presence embodiment may be used in combination with the other of a base, such as aqueous Sodium hydroxide, in a polar embodiments of R. R. R. R. R. R. R. R. R'', R', Q, protic solvent preferably methanol at about -10°C. to about R, L, n, and R''. 10° C. may provide benzyl alcohols 1-3 (Scheme 1, step a). Alternatively, aldehydes 1-2, wherein R is H and R. R. 0.124. In another embodiment R' is C1, Br, CH, or CF. R. R', and Rare as previously disclosed, may be allowed This embodiment may be used in combination with the other to react with trifluorotrimethylsilane in the presence of a embodiments of R', R. R. R. R. R. R. R. R'', R', Q, catalytic amount of tetrabutylammonium fluoride in a polar R, L, n, and R. aprotic solvent preferably tetrahydrofuran (Scheme 1, step b) to provide benzyl alcohols 1-3, wherein R is CF. 0.125. In another embodiment Q is O. This embodiment Subsequently, benzyl alcohols 1-3 may be converted into may be used in combination with the other embodiments of benzyl halides 1-4, wherein E is Br, Cl, or I, and R', R. R. R. R. R. R. R. R. R7, R, R, R, R2, R, L, n, and R. R. R. and Rare as previously disclosed, by treatment R 14. with a halogenating reagent, such as N-bromosuccinimide, 0126. In another embodiment L is CHCH or CH(CH) and triethylphosphite in a solvent that does not react with the CH. This embodiment may be used in combination with the reagents preferably dichloromethane at about 40° C. to other embodiments of R', R. R. R. R. R. R. R. R', provide benzyl halides 1-4, E is Br (Scheme 1, step c). R'', R', Q, R', n, and R''. Alternatively, benzyl alcohols 1-3 may be converted into benzyl halides 1-4, where E is Br by treatment with a 0127. In another embodiment n is 0, 1, or 2. This embodi sulfonyl chloride such as methanesulfonyl chloride in the ment may be used in combination with the other embodi presence of a base Such as triethylamine and Subsequent ments of R', R. R. R. R. R. R. R. R. R'', R', Q, treatment of the resultant sulfonate with a transition metal R, L, and R''. bromide such as iron(III) bromide. Additionally, treatment 0128. In another embodiment R'' is CHCH or CHCF. with chlorinating reagents such as thionyl chloride in the This embodiment may be used in combination with the other presence of a base such as pyridine in a hydrocarbon solvent embodiments of R. R. R. R. R. R. R. R. R. R'', such as toluene at about 110° C. may provide benzyl halides R'', Q, R, L, and n. 1-4, where E is C1 (Scheme 1, step c). US 2017/020880.6 A1 Jul. 27, 2017 13

Scheme 1 R5 O R R7 8. Her R5 OH R5 E R3 RI R6 R6 R R R2 R7 C R7 -e- 1-1 5 R3 R1 R3 R1 R O R2 R2 R R6 b 1-3 1-4 He R3 RI R2 1-2

Preparation of Fluorinated Vinylbenzoic Esters and Acids ranging from about ambient temperature to about 45° C., to provide fluorinated vinyl esters 2-3 (Scheme 2, 0141 Halobenzoic acids 2-1, wherein R. R', R', and step b). Fluorinated vinyl benzoic acid esters 2-3 may be R" are as previously disclosed may be converted to treated with a metal hydroxide source such as lithium halobenzoic acid esters 2-2, wherein R. R', R', and R' hydroxide in a mixed solvent system comprising a polar are as previously disclosed. Halobenzoic acids 2-1, may be aprotic solvent preferably tetrahydrofuran and polar protic treated with an acid, Such as Sulfuric acid, in the presence of solvents preferably methanol and water at about ambient a (C-C)alcohol such as ethanol, to provide halobenzoic temperature to provide fluorinated vinyl benzoic acids 2-4 acid ethyl esters 2-2 (Scheme 2, step a). Fluorinated vinyl (Scheme 2, Step c).

Scheme 2 R9 Br, I R10 Br, I R10 8. --- OH O R12 R12 Nic 1-C8)alkyl R11 O R11 O 2-1 2-2

b

F R9 R9 R10 R10 HC C HC -- R12 OH R12 "Sc-cally RI O R11 O 2-4 2-3 benzoic acid esters 2-3 may be accessed via reaction of 2-2 0142. Alternatively, halobenzoic acids 2-1 may be with a fluorinated vinyl silane in the presence of a palladium directly treated with a vinyl borane source such as vinyltri catalyst Such as tetrakis(triphenylphospine)palladium(0), a fluoroborate or 3-hydroxy-2,3-dimethylbutan-2-yl hydrogen copper additive such as copper(I) iodide, and a fluoride vinylboronate in the presence of a palladium catalyst Such as Source. Such as cesium fluoride in a polar aprotic solvent 1,1'-bis(diphenylphosphino)ferrocene palladium(II) dichlo preferably 1,3-dimethyl-2-imidazolidinone at temperatures ride, and a base such as potassium carbonate, in a polar US 2017/020880.6 A1 Jul. 27, 2017

aprotic solvent preferably dimethylsulfoxide attemperatures -continued ranging from about 80°C. to about 140°C., to provide vinyl R R6 R7 F R9 benzoic acids 3-1, wherein R. R', R', and R'' are as previously disclosed (Scheme 3, step a). Vinyl benzoic acids 3-1 may be treated with bromine source such as N-bromo Succinimide, and a fluorine source Such as triethylamine trihydrofluoride, in a polar aprotic solvent preferably dichlo romethane at about 0° C., to provide bromofluoroalkyl benzoic acids 3-2, wherein R. R', R', and R'' are as previously disclosed (Scheme 3, step b). Bromofluoroalkyl 4-1 benzoic acids 3-2 may be treated with a base such as potassium tert-butoxide, in a polar protic solvent preferably methanol, attemperatures ranging from about 0°C. to about ambient temperature, to provide fluorinated vinyl benzoic Preparation of Phenyl Allylbenzamides acids 2-4 (Scheme 3, step c). 0144 Phenyl allylbenzamides 5-3, wherein R', R. R. R. R. R. R7, R. R. R'', R, R, L, n, and R'' are as Scheme 3 previously disclosed may be prepared by treatment with amines or amine salts 5-2, wherein R, L, n, and R'' are as R9 9 previously disclosed, and activated carboxylic acids 5-1, Br, I R10 R10 wherein A is an activating group, and R', R. R. R. R. R. 8. HC -e- R. R. R', R', and R'' are as previously disclosed, with OH OH a base, such as triethylamine, diisopropylethylamine, or R12 R12 4-methylmorpholine in an anhydrous aprotic solvent such as dichloromethane, tetrahydrofuran, 1.2-dichloroethane, N.N- R11 O R11 O dimethylformamide, or any combination thereof, at tem 2-1 3-1 peratures between about 0° C. and about 120° C. (Scheme 5, step a). 0145 Activated carboxylic acids 5-1 may be an acid halide. Such as an acid chloride, an acid bromide, or an acid F R9 F R9 fluoride; a carboxylic ester, Such as a para-nitrophenyl ester, R10 C Br R10 HC a pentafluorophenyl ester, an ethyl (hydroxyimino)cyanoac 2 se etate ester, a methyl ester, an ethyl ester, a benzyl ester, an R12 OH R12 OH N-hydroxysuccinimidyl ester, a hydroxybenzotriazol-1-yl ester, or a hydroxypyridyltriazol-1-yl ester, an O-acylisou R11 O R11 O rea; an acid anhydride; or a thioester. Acid chlorides may be 2-4 3-2 prepared from the corresponding carboxylic acids by treat ment with a dehydrating chlorinating reagent, Such as oxalyl chloride or thionyl chloride. Activated carboxylic acids 5-1 Preparation of Fluorinated Phenyl Allylbenzoic Acids may be prepared from carboxylic acids in situ with a 0143 Benzyl halides 1-4 and fluorinated vinylbenzoic uronium salt, such as 1-bis(dimethylamino)methylene)-1H acids 2-4 may be treated with a copper(I) source Such as 1,2,3-triazolo 4,5-b]pyridinium 3-oxide hexafluorophos copper(I) chloride or copper(I) bromide and a pyridine phate (HATU), O-(benzotriazol-1-yl)-N.N.N',N'-tetram ligand Such as 2.2-bipyridyl in a polar aprotic solvent ethyluronium hexafluorophosphate (HBTU), or (1-cyano-2- preferably N-methyl-2-pyrrolidone, at a temperature ethoxy-2-oxoethylidenaminooxy)dimethylamino between about 100° C. to about 180° C. to provide fluori morpholino-carbenium hexafluorophosphate (COMU). nated phenylallylbenzoic acids 4-1, wherein R. R. R. R. Activated carboxylic acids 5-1 may also be prepared from R. R. R. R. R', R', and R'' are as previously disclosed carboxylic acids in situ with a phosphonium salt Such as (Scheme 4, Step a). benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluo rophosphate (PyBop). Activated carboxylic acids 5-1 may also be prepared from carboxylic acids in situ with a Scheme 4 coupling reagent Such as 1-(3-dimethylamino propyl)-3- ethylcarbodiimide, or dicyclohexylcarbodiimide in the pres F R9 R5 E R6 ence of a triazole Such as hydroxybenzotriazole.monohy R10 R drate (HOBt) or 1-hydroxy-7-azabenzotriazole (HOAt). HC R7 O-Acylisoureas may be prepared with a dehydrating car -- bodimide such as 1-(3-dimethylamino propyl)-3-ethylcarbo OH R12 R3 R1 diimide or dicyclohexylcarbodiimide. Activated carboxylic acids 5-1 may also be prepared from carboxylic acids in situ R11 O R2 with a coupling reagent such as 2-chloro-1,3-dimethyl imi 2-4 1-4 dazolidinium hexafluorophosphate (CIP) in the presence of a triazole such as 1-hydroxy-7-azabenzotriazole (HOAt). 0146 Phenyl allylbenzamides 5-3, wherein n is 0 (sul fide), may be oxidized to the corresponding Sulfoxide, wherein n is 1, or sulfone, wherein n is 2, by treatment with US 2017/020880.6 A1 Jul. 27, 2017 one equivalent of sodium perborate in a protic Solvent Such as acetic acid (sulfoxide) or two equivalents of sodium perborate (sulfone). Preferably, the oxidation will be per formed at temperatures between about 40°C. to about 100° C. using 1.5 equivalents of sodium perborate to provide chromatographically separable mixtures of Sulfoxide and sulfone diphenyl allylbenzamides 5-3.

oHCI 0149 Phenyl allylbenzamides 5-3 may be exposed to ultraviolet irradiation in a deuterated or non-deuterated Solvent Such as acetone to provide phenyl allylbenzamides 6-1 (Scheme 6, step a). Preparation of Amines and Amine Salts

0150. Amines and amine salts 5-2 may be prepared as outlined in Scheme 7. N-tert-Butoxycarbonyl aminoalcohols 7-1, wherein R and L are as previously disclosed, may be treated with a sulfonyl chloride such as methanesulfonyl chloride or a sulfonyl anhydride such as methanesulfonyl anhydride in the presence of a base Such as triethylamine in a solvent Such as dichloromethane at temperatures from about -20° C. to about 40° C. (Scheme 7, step a). The resultant N-tert-butoxycarbonyl amino sulfonates may then be treated with sodium thioacetate, prepared by treating thioacetic acid with a base Such as sodium hydride, in a polar aprotic solvent such as N,N-dimethylformamide attempera tures from about 10° C. to about 40° C. to provide N-tert butoxycarbonyl amino thioesters 7-2, wherein R' and L are as previously disclosed (Scheme 7, step b). Alkylation of the 0147 Alternatively, phenylallylbenzamides 5-3, wherein N-tert-butoxycarbonyl amino thioesters 7-2 may be accom n is 0 (sulfide), may be oxidized to the corresponding plished in an oxygen free environment by first removing the sulfoxide by treatment with hydrogen peroxide in a protic acetate from the sulfur by treatment with a metal hydroxide Solvent such as methanol or preferably hexafluoroisopropa base such as sodium hydroxide followed by treatment with halides R''-halo, wherein R'' is alkyl, or triflates R''-OTf nol. Preferably, the oxidation will be performed at tempera wherein R'' is alkyl, in a polar protic solvent such as tures between about 10° C. to about 100° C. methanol at temperatures from about -10° C. to about 40° 0148 Amine salts 5-2 may be generated in situ from the C. to provide N-tert-butoxycarbonyl amino sulfides 7-3, corresponding N-tert-butoxycarbonyl amines by treatment wherein R, L, and R'' are as previously disclosed (Scheme with an acid Such as hydrogen chloride. Additionally, amine 7, step c). N-tert-Butoxycarbonyl amino sulfides 7-3 may then be treated with an acid such as hydrogen chloride to salts 5-2 may be free-based in situ in the presence of a base provide amino salts 5-2, wherein n is 0 (Scheme 7, step d). Such as Sodium bicarbonate, triethylamine, or 4-methylmor Optionally, the amine salts 5-2 may be free-based in the pholine during reaction with activated carboxylic acids 5-1 presence of a base such as Sodium bicarbonate or triethyl to provide phenyl allylbenzoic amides 5-3. amine prior to use in Subsequent reactions. US 2017/020880.6 A1 Jul. 27, 2017 16

Scheme 7 R13 R13 a, b HC O N-OH H3C O N- CH3 H3C H3C CH O CH3 O O 7-1 7-2

R13 R (O) dore, d oHC HC O NS 1n 14 HNN 11 SnN R14 H3C L R 5-2 CH, O 7-3 R13 f R13 (O), l SH HN n1 N1 NR 14 7-4 5-2

0151. Alternatively, N-tert-butoxycarbonyl amino sul- C. to provide thioacids 8-3, wherein L and R'' are as fides 7-3, may be oxidized to the corresponding sulfoxide or previously disclosed (Scheme 8, step a). Thioacids 8-3 may sulfone by treatment with one equivalent of sodium perbo then be treated with an azide source such as diphenyl rate in a protic solvent such as acetic acid to provide the phosphorazidate in the presence of a base such as triethyl sulfoxide; or two equivalents of sodium perborate to provide amine in a solvent such as 1,2-dichloroethane at tempera the sulfone (Scheme 7, step e). The resultant sulfones may tures from about 60° C. to about 90° C. to effect a Curtius rearrangement. The resultant isocyanate may be treated with then be treated with an acid such as hydrogen chloride to a benzyl alcohol Such as (4-methoxyphenyl)methanol to provide amine salts 5-2 (Scheme 7, step d). Optionally, the provide benzyl 8-4, wherein R' is H. L., and R' amine salts 5-2 may be free-based in the presence of a base are as previously disclosed (Scheme 8, step b). Benzyl Such as Sodium bicarbonate or triethylamine prior to use in carbamates 8-4 may be treated with an acid such as trifluo Subsequent reactions. roacetic acid followed by salt metathesis with hydrochloric 0152 Amines 5-2 may alternatively be prepared by treat acid to provide amino salts 5-2, wherein R' is H and n is 0 ing aminothiols 7-4, wherein R' and L are as previously (Scheme 8, step c). Optionally, the amine salts 5-2 may be disclosed with a base such as sodium hydride followed by free-based in the presence of a base Such as Sodium bicar treatment with halides R''-halo, wherein R'' is alkyl, or bonate or triethylamine prior to use in Subsequent reactions. triflates R''-OTf, wherein R'' is alkyl, in a polar aprotic 0154 Alternatively, benzyl carbamates 8-4 may be oxi solvent such as N,N-dimethylformamide at temperatures dized to the corresponding sulfone by treatment with two from about 15° C. to about 50° C. (Scheme 7, step f). equivalents of sodium perborate (Scheme 8, step d). The 0153. Thiols 8-2, wherein R'' is as previously disclosed, resultant Sulfones may then be treated with an acid Such as may be treated with a base such as sodium hydride followed hydrogen chloride to provide amino salts 5-2 (Scheme 8, by treatment with acids 8-1, wherein L is as previously step c). Optionally, the amine salts 5-2 may be free-based in disclosed, in a polar aprotic solvent such as N,N-dimethyl the presence of a base Such as Sodium bicarbonate or formamide attemperatures from about -10°C. to about 30° triethylamine prior to use in Subsequent reactions. US 2017/020880.6 A1 Jul. 27, 2017 17

-continued HC R13 R (O) c or d, c 3 oHCI -e- O N S HN N1 S NR 14 r N1 NR 14 5-2 O 8-4

EXAMPLES sulfate, filtered, and concentrated to provide the title com pound as a brown oil (1.40 g. 64%); H NMR (400 MHz, 0155 These examples are for illustration purposes and CDC1,) & 8.03 (d. J=8.2 Hz, 1H), 7.89 (d. J=1.8 Hz, 1H), are not to be construed as limiting this disclosure to only the 7.59 (dd, J=8.3, 1.8 Hz, 1H), 7.43 (s. 2H), 5.83 (dd, J=32.4, embodiments disclosed in these examples. 9.6 Hz, 1H), 4.60 (p. J=8.8 Hz, 1H); 'F NMR (37.6 MHz, 0156 Starting materials, reagents, and solvents that were CDC1) 8 -69.32 (d. J–2.3 Hz), -108.70--119.01 (m): obtained from commercial sources were used without fur ESIMS m/z 505 (IM-HI). ther purification. Anhydrous solvents were purchased as Sure/SealTM from Aldrich and were used as received. Melt 0159. The following compounds were prepared in like ing points were obtained on a Thomas Hoover Unimelt manner to the procedure outlined in Example 1: capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and (Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophenyl) are uncorrected. Examples using "room temperature' were but-1-en-1-yl)-2-(trifluoromethyl)benzoic acid (C2) conducted in climate controlled laboratories with tempera (0160 tures ranging from about 20° C. to about 24°C. Molecules are given their known names, named according to naming programs within ISIS Draw, ChemDraw, or ACD Name Pro. If Such programs are unable to name a molecule, Such molecule is named using conventional naming rules. "H NMR spectral data are in ppm (ö) and were recorded at 300, 400, 500, or 600 MHz: ''C NMR spectral data are in ppm (8) and were recorded at 75, 100, or 150 MHz, and F NMR spectral data are in ppm (Ö) and were recorded at 376 MHz, unless otherwise Stated. Example 1: Preparation of (Z)-2-bromo-4-(1.4.4.4- tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl) benzoic acid (C1) (0161) Isolated as a yellow oil (7.6 g. 68%): 'H NMR (400 MHz, CDC1) & 8.04 (d. J=8.2 Hz, 1H), 7.99-7.94 (m. 1H), O157 7.84 (dd, J=8.2, 1.8 Hz, 1H), 7.44 (s. 2H), 5.90 (dd, J=32.4, 9.6 Hz, 1H), 4.62 (p, J=8.9 Hz, 1H); 'F NMR (37.6 MHz,

CDC1,) & -59.60, -69.28 (d. J=2.3 Hz), -112.11: ESIMS m/Z. 493 (M-HI). (Z)-4-(1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)pent 1-en-1-yl)-2-(trifluoromethyl)benzoic acid (C3) (0162

0158 To a 25 mL round-bottomed flask were added 2,2'-bipyridine (0.255 g, 1.63 mmol), 2-bromo-4-(1-fluoro vinyl)benzoic acid (C24) (1.00 g, 4.08 mmol), and 5-(1- bromo-2.2.2-trifluoroethyl)-1,2,3-trichlorobenzene (2.79 g, 8.16 mmol) in N-methylpyrrolidone (2.0 mL) to give a yellow solution. Copper(I) bromide (0.117 g. 0.816 mmol) was added and the reaction mixture was purged with nitro gen for 5 minutes. The reaction was then heated to 150° C. for 3 hours. The reaction mixture was poured into ice water (0163) Isolated as a yellow foam (0.628 g. 60%): 'H NMR (100 mL). The water was filtered and the resultant black gum (400 MHz, CDC1) & 8.00 (d. J=8.2 Hz, 1H), 7.95 (d. J=8.8 was dissolved in ethyl acetate (800 mL), washed with brine HZ, 1H), 7.81 (d. J=8.3 Hz, 1H), 7.42 (s. 2H), 5.96 (dd. (2x200 mL), and water (2x200 mL), dried over magnesium J=33.6, 9.8 Hz, 1H), 4.29 (td, J=14.3, 9.8 Hz, 1H), 1.65 (t,

US 2017/020880.6 A1 Jul. 27, 2017 22

0205 To a 25 mL vial was added (Z)-4-(1,4,4,4-tetra 2-Chloro-4-(1-fluorovinyl)benzoic acid (C26) fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluo romethyl)benzoic acid (C2) (0.200 g, 0.404 mmol), oxalyl 0211 chloride (0.095 mL, 1.09 mmol), and N,N-dimethylforma mide (catalytic amount) in dichloromethane (1.3 mL) to give a yellow solution. The reaction was stirred for 15 hours at room temperature. The solvent was removed under vacuum C providing the title compound as a yellow gum (0.220 g, HC 95%): 'HNMR (400 MHz, CDC1) & 7.99 (d. J=8.2 Hz, 1H), OH 7.92 (d. J=1.7 Hz, 1H), 7.81 (dd, J=8.2, 1.8 Hz, 1H), 7.44 (s, 2H), 5.88 (dd, J=32.5, 9.6 Hz, 1H), 4.73-4.50 (m. 1H); 'F NMR (37.6 MHz, CDC1) & -59.58, -69.32, -109.75-113. O 19 (m); IR (thin film) 3445, 2925, 1646, 1275, 749 cm; ESIMS m/z 476 (IM-Cl"). 0212) Isolated as a white solid (3.5 g, 75%): 'H NMR (400 MHz, acetone-d) & 7.97 (dd, J=8.2, 0.9 HZ, 1H), 7.76 Example 5: Preparation of (d. J=1.7 Hz, 1H), 7.70 (dd, J=8.2, 1.7 Hz, 1H), 5.68-5.45 2-bromo-4-(1-fluorovinyl)benzoic acid (C24) (m. 1H), 5.11 (dd, J=18.2, 4.1 Hz, 1H); F NMR (376 MHz, 0206 acetone-d) 8 -108.71; ESIMS m/z 200 (IM-HI). 4-(1-Fluorovinyl)-2-methylbenzoic acid (C27) F 0213 Br HC F OH CH3 HC O OH 0207. To a 250 mL round-bottomed flask were added methyl 2-bromo-4-(1-fluorovinyl)benzoate (C29) (1.8 g., 7.0 O mmol), lithium hydroxide hydrate (0.88 g. 21 mmol), metha nol (7.0 mL), tetrahydrofuran (21 mL), and water (7.0 mL), 0214) Isolated as a white solid (0.550 g, 89%); H NMR and the reaction mixture was stirred overnight at room (400 MHz, methanol-d) & 7.92 (d. J–8.1 Hz, 1H), 7.59-7.52 temperature. The mixture was concentrated, quenched with (m. 1H), 7.52-744 (m. 1H), 5.29 (dd, J=50.1, 3.7 Hz, 1H), a pH 4 buffer, and extracted with ethyl acetate to provide the 4.93 (dd, J=18.1, 3.7 Hz, 1H), 2.60 (s, 3H); F NMR (376 title compound as a white solid (1.0 g, 56%): "H NMR (400 MHz, methanol-da) 8 -110.32 (d. J–2.1 Hz); ESIMS m/z MHz, CDC1) & 8.01 (d. J=8.2 Hz, 1H), 7.89 (d. J=1.8 Hz, 181 (IM+H"). 1H), 7.57 (dd, J=8.3, 1.8 Hz, 1H), 5.21 (dd, J=48.6, 4.0 Hz, 1H), 5.06 (dd, J=17.3, 3.9 Hz, 1H); F NMR (471 MHz, Example 6: Preparation of methyl CDC1) 8-108.71 (d. J–14 Hz); ESIMS m/z 244 (M-HI). 4-(1-fluorovinyl)-2-(trifluoromethyl)benzoate (C28) 0208. The following compounds were prepared in like manner to the procedure outlined in Example 5: 0215 4-(1-Fluorovinyl)-2-(trifluoromethyl)benzoic acid (C25) 0209 HC F

F F F HC F OH 0216) To a 100 mL round-bottomed flask was added methyl 4-bromo-2-(trifluoromethyl)benzoate (2.25 g, 8.00 mmol), (1-fluorovinyl)(methyl)diphenylsilane (3.58 g. 14.8 O mmol), and 1,3-dimethylimidazolidin-2-one (40 mL). Tet rakis(triphenylphosphine)palladium(0) (0.459 g, 0.400 0210. Isolated as a white solid (1.9 g, 93%); H NMR mmol), copper(I) iodide (0.0760 mg, 0.400 mmol), and (400 MHz, methanol-d) & 7.95 (d. J=1.5 Hz, 1H), 7.95-7.91 cesium fluoride (3.62 g, 23.9 mmol) were added and the (m. 1H), 7.90-7.86 (m. 1H), 5.46 (dd, J=50.0, 4.1 Hz, 1H), reaction was stirred at room temperature for 24 hours under 5.09 (dd, J=18.0, 4.1 Hz, 1H); F NMR (37.6 MHz, metha a nitrogen atmosphere. Water was added to the mixture and nol-da) 8 -61.04 (d. J=1.1 Hz), -110.93: ESIMS m/Z 233 the mixture was diluted with 3:1 hexanes/diethyl ether. The (M-HI). layer was separated, and the organic layer was dried over US 2017/020880.6 A1 Jul. 27, 2017

Sodium sulfate, concentrated, and the residue purified by 0223) Isolated as a colorless oil (0.5 g., 85%): 'H NMR flash column chromatography provided the title compound (400 MHz, methanol-d) & 7.90 (d. J–8.2 Hz, 1H), 7.51 (s, as a colorless oil (2.00 g.96%): 'H NMR (400 MHz, CDC1) 1H), 7.49 (dd, J=8.0, 1.6 Hz, 1H), 5.30 (dd, J=50.1, 3.7 Hz, & 7.96-7.87 (im, 1H), 7.83 (dq, J=8.1, 0.7 Hz, 1H), 7.77 (dd, 1H), 4.95 (dd, J=18.0, 3.7 Hz, 1H), 3.88 (d. J=5.9 Hz, 3H), J=8.2, 1.7 Hz, 1H), 5.23 (dd, J=48.6, 4.0 Hz, 1H), 5.07 (dd, 2.59 (s.3H); 'F NMR (37.6 MHz, methanol-da) 8 -110.41 J=17.4, 4.0 Hz, 1H), 3.95 (s, 3H); 19F NMR (376 MHz, (d. J=1.3 Hz); ESIMS m/z 195 (IM+H"). CDC1) & -59.92, -108.73 (d. J=1.4 Hz); EIMS m/z 248 Example 7: Preparation of (IMI). 0217. The following compounds were prepared in like 4-(1-fluorovinyl)-2-(trifluoromethyl)benzoic acid manner to the procedure outlined in Example 6: (C25) 0224 Methyl 2-bromo-4-(1-fluorovinyl)benzoate (C29)

0218 F F F

HC F

Br OH HC O O n CH3 OXat a Step 1: 4-(2-bromo-1-fluoroethyl)-2-(trifluorom ethyl)benzoic acid (C32) 0219. Isolated as a colorless oil (1.8 g., 93%); H NMR 0225 2-(Trifluoromethyl)-4-vinylbenzoic acid (5.3.g. 24 (400 MHz, CDC1) & 7.84 (d. J=1.7 Hz, 1H), 7.82 (dd, J=8.2, mmol) was dissolved in dichloromethane (123 mL) at 0°C., 0.9 Hz, 1H), 7.50 (d. J=1.5 Hz, 1H), 5.16 (dd, J=48.7, 3.9 triethylamine trihydrofluoride was added (8.0 mL, 49 mmol) HZ, 1H), 5.01 (dd, J=17.3, 3.9 Hz, 1H), 3.94 (d. J–2.2 Hz, followed by N-bromosuccinimide (8.7 g. 49 mmol). The 3H); 'F NMR (37.6 MHz, CDC1) 8 -108.61 (d. J=1.5 Hz); reaction mixture was stirred for 16 hours while warming to ESIMS m/z 258 (IM-HI). room temperature. Water was then added to the mixture, washed with dichloromethane, dried over sodium sulfate, Methyl 2-chloro-4-(1-fluorovinyl)benzoate (C30) filtered, and concentrated providing the title compound as a 0220 yellow oil which was used without further purification (5.0 g, 65%). Step 2: 4-(1-fluorovinyl)-2-(trifluoromethyl)benzoic acid (C25) C 0226 4-(2-Bromo-1-fluoroethyl)-2-(trifluoromethyl) HC benzoic acid (4.3 g, 14 mmol) was dissolved in methanol (68 O mL) at 0° C. and potassium tert-butoxide (4.6 g. 41 mmol) n CH3 was added as a solid while stirring. The reaction mixture was OYearXa allowed to slowly warm to 23° C. and then stirred for 4 hours. Hydrochloric acid (1 N) was slowly added, and the mixture was extracted with ethyl acetate. Purification by 0221) Isolated as a colorless oil (2.1 g, 99%): "H NMR flash column chromatography using 0-40% acetone in (400 MHz, CDC1) & 7.86 (dd, J=8.2, 0.9 Hz, 1H), 7.64 (d. hexanes provided the title compound as an off-white solid J=1.7 Hz, 1H), 7.48 (dd, J=8.3, 1.8 Hz, 1H), 5.17 (dd, (1.7 g 53%): 'H NMR (400 MHz, CDC1) & 8.02 (d. J=8.2 J=48.7, 3.8 Hz, 1H), 5.02 (dd, J=17.3, 3.9 Hz, 1H), 3.94 (s, HZ, 1H), 8.00-7.93 (m, 1H), 7.82 (dd, J=8.2, 1.8 Hz, 1H), 3H): 'F NMR (376 MHz, CDC1,) 8-108.63 (d. J=1.4 Hz); 5.27 (dd, J–48.5, 4.1 Hz, 1H), 5.11 (dd, J=17.3, 4.1 Hz, 1H): ESIMS m/z 214 (IM-HI). 0227. The following compounds were prepared in like manner to the procedure outlined in Example 7: Methyl 2-chloro-4-(1-fluorovinyl)benzoate (C31) 4-(1-Fluorovinyl)benzoic acid (C33) 0222 0228

CH HC HC OH CH US 2017/020880.6 A1 Jul. 27, 2017 24

0229 Isolated as a white solid (6.5 g, 86%); H NMR 0234. The following compounds were prepared in like (400 MHz, CDC1) & 8.13 (d. J=8.2 Hz, 2H), 7.69-7.62 (m, manner to the procedure outlined in Example 8: 2H), 5.21 (dd, J=49.0, 3.7 Hz, 1H), 5.02 (dd, J=17.5, 3.7 Hz, 1H); F NMR (376 MHz, CDC1,) 8 -108.35; ESIMS m/z 1,3-Dibromo-5-(1-bromo-2,2,2-trifluoroethyl)-2- 165 (IM-HI). chlorobenzene (C35) 4-(1-Fluorovinyl)-2-methylbenzoic acid (C27) 0235

0230 F F F F Br CH3 Br HC

OH C

Br O 0236) Isolated as a clear oil (28 g. 56%); H NMR (400 0231. Isolated as a colorless oil (0.165 g, 89%); H NMR MHz, DMSO-d) & 8.01-7.97 (m, 2H), 6.26-6.20 (m. 1H): (400 MHz, CDC1) & 8.12-8.03 (m, 1H), 7.46 (dd, J=5.8.2.1 IR (thin film) 1168, 736, 557 cm; ESIMS m/z 428 (M+ Hz, 2H), 5.17 (dd, J=49.1, 3.7 Hz, 1H), 4.98 (dd, J=17.5, 3.7 HI). HZ, 1H), 2.68 (s, 3H); 'F NMR (376 MHz, CDC1,) 5-108. 50. 5-(1-Bromo-2.2.2-trifluoroethyl)-2-chloro-1,3-dim ethylbenzene (C36) Example 8: Preparation of 5-(1-bromo-2,2-difluoro propyl)-1,2,3-trichlorobenzene (C34) 0237) 0232 F F F

H3C Br

F C CH3 C Br 0238 Isolated as a clear oil (6.32g, 89%); H NMR (300 MHz, DMSO-d) & 7.39 (s. 2H), 6.17-6.09 (m. 1H), 2.35 (s, C 6H); IR (thin film) 1114, 754 cm; ESIMS m/z. 302 (M+ C HI). 2-Bromo-5-(1-bromo-2.2.2-trifluoroethyl)-1,3-di chlorobenzene (C37) 0239) 0233 N-Bromosuccinimide (12.0 g. 67.5 mmol) was added to a solution of 2,2-difluoro-1-(3,4,5-trichlorophenyl) F propan-1-ol (C43) (6.00 g, 21.8 mmol) in dichloromethane F F (72.6 mL). To this stirred solution was added triphenyl phosphite (17.1 mL, 65.3 mmol) slowly, dropwise, and the C reaction mixture became dark brown. The reaction mixture Br was then heated at reflux for 3 hours. The solvent was concentrated, and the residue was triturated with diethyl ether. The solid was filtered, the filtrate was concentrated Br and the resultant oil was purified by flash column chroma tography using hexanes as eluent to provide the title com C pound as a clear and colorless oil (2.20g, 25%); H NMR (400 MHz, CDC1) & 7.52 (s. 2H), 4.85 (dd, J=12.3, 10.4 Hz, 0240 Isolated as a clear oil (19 g, 46%); H NMR (400 1H), 1.77 (t, J=18.2 Hz, 3H); F NMR (376 MHz, CDC1) MHz, CDC1) & 7.54-7.51 (m, 2H), 5.03-4.98 (m. 1H); 'F 8 -92.14-95.01 (m); EIMS m/z 338 (MI"). NMR (376 MHz, CDC1) 8 -70.38. US 2017/020880.6 A1 Jul. 27, 2017

4-(1-Bromo-2,2-difluoropropyl)-1,2-dichlorobenzene 4-(1-Bromo-2.2.2-trifluoroethyl)-1-chloro-2-fluo (C38) robenzene (C41) 0241 0247

F F F F

F Br Br

C C

0242 Isolated as a colorless liquid (1.40 g. 65%); H 0248 Isolated as a yellow oil (1.1 g, 45%): 'H NMR (400 NMR (300 MHz, DMSO-d) & 7.76-7.70 (m, 2H), 7.54 (dd, MHz, CDC1,) & 7.44 (dd, J=8.3, 7.5 Hz, 1H), 7.34 (dd. J=8.4, 1.8 Hz, 1H), 5.81-5.73 (m, 1H), 1.67 (d. J=18.9 Hz, J=9.5, 1.9 Hz, 1H), 7.26-7.22 (m, 1H), 5.08 (q, J=7.1 Hz, 3H); IR (thin film) 1118, 800, 499 cm; EIMS m/z 304 1H); EIMS m/z 291 (MI"). (IMI). Example 9: Preparation of 5-(1-bromo-2,2-difluo 2-Bromo-4-(1-bromo-2,2,2-trifluoroethyl)-1-chlo robutyl)-1,2,3-trichlorobenzene (C42) robenzene (C39) 0249 0243

F F F CH Br F Br F

C C Br

C

C 0244 Isolated as a colorless liquid (10.5 g, 54%); H NMR (400 MHz, CDC1,) & 7.76 (d. J=1.2 Hz, 1H), 7.49 7.47 (m. 1H), 7.41-7.39 (m, 1H), 5.07-5.02 (m, 1H); IR (thin film) 3437, 2924, 1631, 1114 cm; EIMS m/z. 350 (MI). 0250 Triethylamine (2.46 mL, 17.6 mmol) and methane 4-(1-Bromo-2.2.2-trifluoroethyl)-2-chloro-1-fluo sulfonyl chloride (1.10 mL, 14.1 mmol) were added to a robenzene (C40) solution of 2,2-difluoro-1-(3,4,5-trichlorophenyl)butan-1-ol (C44) (3.40 g, 11.7 mmol) in dichloromethane (58.7 mL). 0245 The reaction mixture was stirred for 1 hour, and then pentane was added. Filtration followed by concentration of the filtrate under vacuum provided a white solid. The solid was F dissolved in dichloromethane (58.7 mL) to which iron(III) F F bromide (6.94 g, 23.5 mmol) was added. The reaction mixture was stirred overnight. The mixture was poured into C water and then extracted with dichloromethane. The organ Br ics were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column F chromatography using hexanes as eluent provided the title compound as a white solid (3.52 g, 72%); H NMR (400 MHz, CDC1) & 7.51 (s. 2H), 4.85 (t, J=12.1 Hz, 1H), 0246) Isolated as a colorless oil (8.0 g, 73%); H NMR 2.14-191 (m, 2H), 1.06 (t, J–7.5 Hz, 3H); 'C NMR (101 (300 MHz, CDC1) & 7.59-7.57 (m, 1H), 742-7.33 (m, 1H), MHz, CDC1) & 135.55, 134.39, 132.52, 129.48, 120.25 (t, 7.20-7.14 (m, 1H), 5.10-5.03 (m, 1H); IR (thin film) 3429, J=249.0 Hz), 49.76 (t, J=30.3 Hz), 28.03 (t, J=25.2 Hz), 6.06 2926, 1502, 750 cm; ESIMS m/z 292 (M+H"). (t, J=5.1 Hz); ESIMS m/z 351 (M-HI). US 2017/020880.6 A1 Jul. 27, 2017 26

Example 10: Preparation of 1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-ol 2,2-difluoro-1-(3,4,5-trichlorophenyl)propan-1-ol (C45) (C43) 0256 0251

F HC F C OH C OH C

C 0257) Isolated as a clear and colorless oil (2.78 g. 89%): C "H NMR (400 MHz, CDC1) & 7.57 (dd, J=2.0, 0.9 Hz, 1H), 7.46 (d. J=8.3 Hz, 1H), 7.33-7.27 (m. 1H), 4.83 (td, J=8.9, 3.7 Hz, 1H), 2.55 (dt, J–3.8, 1.1 Hz, 1H), 1.50 (t, J=18.9 Hz, 3H); F NMR (376 MHz, CDC1) 8 -99.52 (d. J=249.6 Hz), -101.09 (d, J-249.4 Hz); IR (thin film) 3417 cm. Example 11: Preparation of 1-(3-bromo-4-chlorophenyl)-2.2.2-trifluoroethanol 0252) 2,2-Difluoro-1-(3,4,5-trichlorophenyl)propan-1- (C46) one (C52) (1.75 g. 6.40 mmol) was dissolved in methanol 0258 (64.0 mL) at room temperature and sodium borohydride F (0.290 g, 7.68 mmol) was added. The reaction was stirred at F F room temperature for 1 hour, until gas evolution ceased. The reaction mixture was poured into water and extracted with Br diethyl ether. The organic layer was washed with brine, dried OH over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-30% acetone in hexanes as eluent provided the title compound as a clear, C colorless oil (1.60 g, 91%): "H NMR (400 MHz, CDC1) & (0259 Trimethyl(trifluoromethyl)silane (10.1 mL, 68.4 7.50 (d. J=0.9 Hz, 2H), 4.81 (td, J=8.7, 3.8 Hz, 1H), mmol) and tetrabutylammonium fluoride (1.44 g. 4.56 mmol) were added to a stirred solution of 3-bromo-4-chloro 1.65-141 (m, 3H); 'F NMR (376 MHz, CDC1,) 8 -98. benzaldehyde (10.0 g, 45.6 mmol) in tetrahydrofuran (150 54-101.73 (m); IR (thin film) 3405, 1555, 1389 cm. mL) at room temperature and the reaction mixture was 0253) The following compounds were prepared in like stirred for 2 hours. The reaction mixture was diluted with manner to the procedure outlined in Example 10: dichloromethane and washed with hydrochloric acid (2 N). The separated organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to afford the 2,2-Difluoro-1-(3,4,5-trichlorophenyl)butan-1-ol title compound as a brown liquid that was used without (C44) further purification (13.2 g, 94%): 10260 "H NMR (300 MHz, CDC1) & 7.76 (s, 1H), 0254 7.50-748 (m. 1H), 7.38-7.35 (m, 1H), 5.03-4.97 (m, 1H), 2.95 (brs, 1H); IR (thin film) 3406, 2881, 1469, 814 cm': EIMS m/z 288 (MI"). CH 0261 The following compounds were prepared in like F manner to the procedure outlined in Example 11: F 1-(3,5-Dibromo-4-chlorophenyl)-2, C 2.2-trifluoroethanol (C47) OH 0262

C F C F F

Br 0255 Isolated as a clear and colorless oil (3.4g, 48%): 'H OH NMR (400 MHz, CDC1) & 7.48 (d. J=0.9 Hz, 2H), 4.87 4.70 (m. 1H), 2.54 (dt, J=4.0, 1.0 Hz, 1H), 2.06-1.82 (m, 1H), 1.82-1.63 (m, 1H), 1.02 (t, J–7.5 Hz, 3H); 'C NMR C (101 MHz, CDC1) & 136.85, 134.20, 131.60, 127.54, 123. Br 19 (t, J=248.0 Hz), 73.71 (t, J=30.0 Hz), 25.05 (t, J=24.6 Hz), 5.35 (t, J=5.2 Hz); EIMS m/z 287 (MI"). US 2017/020880.6 A1 Jul. 27, 2017 27

0263) Isolated as a pale yellow liquid (7.4g, 85%); H 10269. Isolated as a clear and brown gum (7.0g, 97%); H NMR (400 MHz, DMSO-d) & 7.90 (s. 2H), 7.24 (d. J=5.2 NMR (300 MHz, CDC1) & 7.58-7.55 (m, 1H), 7.38-7.33 (m, HZ, 1H), 5.33 (d. J=6.4 Hz, 1H); IR (thin film) 3370, 1175, 1H), 7.20-7.15 (m, 1H), 5.03-4.97 (m, 1H); EIMS m/z 228 735, 541 cm; EIMS m/z. 366 (IMI). (IMI). 1-(4-Chloro-3,5-dimethylphenyl)-2.2.2-trifluoroetha 1-(4-Chloro-3-fluorophenyl)-2.2.2-trifluoroethanol nol (C48) (C51) 0264 0270

F F F F F F

HC F OH OH

C C CH 0271 Isolated as a clear and colorless oil (1.97g, 75%): "H NMR (400 MHz, CDC1,) & 7.52-7.37 (m, 1H), 7.32 (d. 0265 Isolated as a clear liquid (5.0 g, 70%): 'H NMR J=9.6 Hz, 1H), 7.21 (d. J=8.3 Hz, 1H), 5.03 (dd, J=6.3, 3.6 (400 MHz, CDC1) & 7.18 (s. 2H), 4.95-4.92 (m. 1H), 2.40 HZ, 1H), 2.62 (d. J=4.0 Hz, 1H); 'C NMR (101 MHz, (s, 6H); IR (thin film) 3378, 1124, 833 cm; EIMS m/z 238 CDC1) & 158.06 (J-250.4 Hz), 134.40 (d. J–6.6 Hz), (IMI). 130.79, 123.83 (d. J–3.5 Hz), 122.4 (q, J-188.9 Hz), 115.8 (d. J–25.3 Hz), 71.65 (q, J-31.6 Hz); EIMS m/z 228 1-(4-Bromo-3,5-dichlorophenyl)-2.2.2-trifluoroetha (IMI). nol (C49) Example 12: Preparation of 0266 2,2-difluoro-1-(3,4,5-trichlorophenyl) propan-1-one (C52) F 0272 F F

C F OH HC F

Br C O C C 0267 Isolated as a clear oil (33 g, 86%); H NMR (400 C MHz, CDC1) & 7.51 (s. 2H), 5.01-4.96 (m. 1H), 4.14-4.09 (m. 1H); F NMR (376 MHz, CDC1) 8 -78.32. (0273 To 5-bromo-1,2,3-trichlorobenzene (2.28 g, 8.76 mmol) dissolved in diethyl ether (39.8 mL) at -78°C. under 1-(3-Chloro-4-fluorophenyl)-2.2.2-trifluoroethanol nitrogen was added n-butyllithium (3.50 mL, 8.76 mmol). (C50) The solution was stirred for 30 minutes. To this was added ethyl 2,2-difluoropropanoate (1.10 g, 7.96 mmol, as a 20% 0268 w/w solution in toluene) dropwise over 10 minutes, and the reaction mixture was stirred for an additional hour. Saturated F aqueous ammonium chloride solution was added to the F F mixture and stirring was continued as the reaction flask warmed to room temperature. The reaction mixture was then C extracted with diethyl ether, washed with water and brine, OH dried over sodium sulfate, filtered, and concentrated. Puri fication by flash column chromatography provided the title compound as a pale yellow oil (1.76g, 73%); H NMR (400 F MHz, CDC1) & 8.11 (d. J=0.9 Hz, 2H), 1.89 (t, J=19.6 Hz, 3H); F NMR (376 MHz, CDC1,) 8 -92.66: ESIMS m/z 271 (M-HI). US 2017/020880.6 A1 Jul. 27, 2017 28

0274 The following compounds were prepared in like romethyl)benzoic acid (C2) (0.100 g, 0.202 mmol), (R)-1- manner to the procedure outlined in Example 12: ((2.2.2-trifluoroethyl)thio)propan-2-amine hydrochloride (0.0635 g, 0.303 mmol), benzotriazol-1-yl-oxytripyrrolidi 2,2-Difluoro-1-(3,4,5-trichlorophenyl)butan-1-one nophosphonium hexafluorophosphate (0.158 g. 0.303 (C53) mmol), and dichloromethane (4.0 mL). Triethylamine (0.113 mL, 0.807 mmol) was added, and the reaction mixture was 0275 stirred at room temperature overnight. The reaction mixture was concentrated and purified by flash column chromatog raphy to provide the title compound as a yellow oil (0.104 CH3 F g, 75%). 0281. The following compounds were prepared in like F manner to the procedure outlined in Example 13: C O 2-Methyl-4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlo rophenyl)but-1-en-1-yl)-N-((R)-1-((2.2.2-trifluoro C ethyl)thio)propan-2-yl)benzamide (F4) C 0282

0276 Isolated as an oil (2.3 g. 68%) and used without further purification or characterization. 1-(3,4-Dichlorophenyl)-2,2-difluoropropan-1-one (C54) (0277

F HC F 0283) Isolated as a yellow oil (0.120g, 84%). 2-Bromo C 4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1- O en-1-yl)-N-((R)-1-((2.2.2-trifluoroethyl)thio)propan-2-yl) benzamide (F7) C

0278 Isolated as a colorless oil (3.89 g, 71%): 'H NMR (400 MHz, CDC1,) & 8.21-8.18 (m. 1H), 7.99-7.93 (m. 1H), 7.59 (dd, J=8.4, 4.2 Hz, 1H), 1.89 (t, J=19.6 Hz, 3H); 'F NMR (376 MHz, CDC1,) 8 -92.08-93.21 (m); EIMS m/z 238/240 (MI). Example 13: Preparation of 4-((Z)-1,4,4,4-tetra fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N- ((R)-1-((2.2.2-trifluoroethyl)thio)propan-2-yl)-2- (0284) Isolated as a yellow oil (0.158 g, 57%). 2-Chloro (trifluoromethyl)benzamide (F1) 4-((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1- 0279 en-1-yl)-N-((R)-1-((2.2.2-trifluoroethyl)thio)propan-2-yl) benzamide (F10)

F F CH^^k F

0280. To a 25 mL vial were added (Z)-4-(1,4,4,4-tetra fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluo 0285 Isolated as a colorless gum (0.281 g, 80%).

US 2017/020880.6 A1 Jul. 27, 2017 30

4-((Z)-1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)hex 2-Bromo-4-((Z)-3-(3,4-dichlorophenyl)-1,4,4,4-tet 1-en-1-yl)-N-((R)-1-((2.2.2-trifluoroethyl)sulfonyl) rafluorobut-1-en-1-yl)-N-((R)-1-((2.2.2-trifluoro propan-2-yl)-2-(trifluoromethyl)benzamide (F38) ethyl)thio)propan-2-yl)benzamide (F58) 0298 0304

CH3 F F F F F C 21 F H H O F N F C N1){ukS - s1. F C O CH, O CH3 F

0299 Isolated as a white gum (0.052 g, 63%). (0305 Isolated as a yellow gum (0.180 g, 59%). 4-((Z)-1,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)hex Example 14: Preparation of 4-((Z)-3-(3,5-dichloro 1-en-1-yl)-N-((R)-1-((2.2.2-trifluoroethyl)thio) phenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)-N-((R)-1- propan-2-yl)-2-(trifluoromethyl)benzamide (F39) ((2.2.2-trifluoroethyl)sulfonyl)propan-2-yl)-2-(trif luoromethyl)benzamide (F17) 0300 (0306

CH3 F F F F F C

H Croc N F C 1s-nk F C O CH F

0301 Isolated as a white glass (0.056 g. 71%). (0307 Diisopropylethylamine (0.0560 g, 0.430 mmol), 4-((Z)-3-(3,4-Dichlorophenyl)-1,4,4-trifluoropent-1- 2-chloro-1,3-dimethyl imidazolidinium hexafluorophos en-1-yl)-N-((R)-1-((2.2.2-trifluoroethyl)thio)pro phate (0.109 g, 0.390 mmol), and 1-hydroxy-7-azabenzotri pan-2-yl)-2-(trifluoromethyl)benzamide (F57) azole (0.089 g, 0.390 mmol) were added to a solution of (Z)-4-(3-(3,5-dichlorophenyl)-1,4,4,4-tetrafluorobut-1-en 0302) 1-yl)-2-(trifluoromethyl)benzoic acid (C6) (0.180 g, 0.390 mmol), and (R)-1-((2.2.2-trifluoroethyl)sulfonyl)propan-2- amine hydrochloride (C56) (0.0881 g, 0.430 mmol) in dichloromethane (5.0 mL). The reaction mixture was stirred at room temperature for 6 hours. The reaction mixture was diluted with dichloromethane and washed with hydrochloric F acid (2 N) and aqueous Sodium bicarbonate. The organic ^^k F layer was separated, washed with water, dried over Sodium CH F sulfate, filtered, and concentrated. Purification by flash col umn chromatography provided the title compound as a white 0303) Isolated as a white gum (0.060 g, 75%). solid (0.110 g, 42%).

US 2017/020880.6 A1 Jul. 27, 2017 40

(0.167 g, 2.26 mmol) and water (2 mL) were added and the 20.0 mmol) and stirred overnight. The resulting Suspension vial was vortexed followed by stirring for 1 hour. The was concentrated to provide the title compound as a brown prepared acid chloride was dissolved in tetrahydrofuran (5 solid (0.232 g,93%); H NMR (400 MHz, DMSO-d) & 8.44 mL) and the amine Solution was added with stirring. The (s, 3H), 4.93 (qd, J=10.1, 2.7 Hz, 2H), 3.86-3.69 (m, 2H), reaction was concentrated, diluted with ethyl acetate, and 3.66-3.55 (m, 1H), 1.41 (d. J=6.3 Hz, 3H); 'C NMR (101 washed with , water, and brine. The resulting MHz, DMSO-d) & 122.13 (q, J-277.1 Hz), 57.08, 54.66 organic solution was dried over magnesium sulfate, filtered, (q, J-29.7 Hz), 41.39, 18.51; F NMR (37.6 MHz, and concentrated. Purification by flash column chromatog DMSO-d) & -59.43. raphy using 50% ethyl acetate in hexanes as eluent provided the title compound as a brown oil (0.868 g, 76%). Example 20: Preparation of (R)-tert-butyl (1-((2.2, 2-trifluoroethyl)thio)propan-2-yl) (C57) Example 18: Preparation of (Z)-4-(1,4,4,4-tetra fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(2- 0423 ((2.2.2-trifluoroethyl)sulfonyl)ethyl)-2-(trifluorom ethyl)benzamide (F49) and (Z)-4-(1,4,4,4- H tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)- HC O N F S N-(2-((2.2.2-trifluoroethyl)sulfinyl)ethyl)-2- H3C F (trifluoromethyl)benzamide (F50) CH, O CH F 0419 0424. To a 100 mL round-bottomed flask was added

potassium hydroxide (0.465 g, 8.29 mmol) in degassed methanol (16.0 mL). (R) S-(2-((tert-Butoxycarbonyl) amino)propyl)ethanethioate (C58) (1.50 g, 5.53 mmol) was added followed by 2.2.2-trifluoroethyl trifluoromethanesul fonate (2.57 g, 11.1 mmol). The reaction was stirred over night at room temperature. The reaction mixture was con centrated. The residue was diluted with water and ethyl acetate. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated. Purifi cation by flash column chromatography using 0-30% ethyl acetate in hexanes provided the title compound as a colorless liquid (1.07 g. 60%): 1H NMR (400 MHz, CDC1) & 4.54 (s, 1H), 3.86 (s, 1H), 3.13 (qd, J=9.9, 2.6 Hz, 2H), 2.77 (d. J=5.9 Hz, 2H), 1.45 (s.9H), 1.22 (dd, J=6.7, 1.4 Hz, 3H); 'F NMR (37.6 MHz, CDC1) 8 -66.56; IR (thin film) 3340, 2978, 2934, 1687, 1505 cm. 0420. To a 25 mL vial was added (Z)-4-(1,4,4,4-tetra Example 21: Preparation of (R)—S-(2-((tert-bu fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N-(2-((2.2.2- toxycarbonyl)amino)propyl) ethanethioate (C58) trifluoroethyl)thio)ethyl)-2-(trifluoromethyl)benzamide (F51) (0.795 g, 1.25 mmol) and acetic acid (8.32 mL). 0425 Sodium perborate (0.288 g, 1.87 mmol) was added and the reaction was heated at 55° C. The reaction mixture was concentrated with heptanes at 40° C. to azeotrope the acetic O acid. Purification by flash column chromatography using H3C O NH ls 0-100% ethyl acetate in hexanes as eluent provided the title S CH compound (F49) as a colorless oil (0.113 g, 12%) and the H3C title compound (F50) as a colorless oil (0.190g, 21%). CH, O CH3 Example 19: Preparation of (R)-1-((2.2.2-trifluoro 0426 To a 100 mL round-bottomed flask was added ethyl)sulfonyl)propan-2-amine hydrochloride (C56) ethanethioic S-acid (2.23 mL, 31.6 mmol) and N,N-dimeth ylformamide (22.6 mL) which was placed under a nitrogen 0421 atmosphere. Sodium hydride (60% in oil, 1.14 g. 28.4 mmol) was added portionwise and the orange solution was stirred O F for 15 minutes. (R)-2-((tert-Butoxycarbonyl)amino)propyl methanesulfonate (C59) (4.00 g, 15.8 mmol) was added and S the reaction mixture was stirred. The reaction was diluted 0 HCI CH1) /M {uk F with ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate (2x). The combined organic layers was washed with water (2x), brine, 0422 (R)-tert-Butyl (1-((2.2.2-trifluoroethyl)sulfonyl) dried over magnesium Sulfate, filtered, and concentrated. propan-2-yl)carbamate (C57) (0.300 g, 0.983 mmol) was Purification by flash column chromatography using 0-50% treated with hydrogen chloride (4 M in dioxane, 5.00 mL. ethyl acetate in hexanes provided the title compound as an US 2017/020880.6 A1 Jul. 27, 2017 41 off-white solid (1.29 g, 33%): 'H NMR (400 MHz, CDC1) 0428 To a 250 mL round-bottomed flask was added & 4.61 (s, 1H), 4.04-3.65 (m. 1H), 3.13-2.92 (m, 2H), 2.36 (R)-tert-butyl (1-hydroxypropan-2-yl)carbamate (1.15 g. (s.3H), 1.44 (s, 9H), 1.17 (d. J=6.7 Hz, 3H); C NMR (101 6.56 mmol) and dichloromethane (26.3 mL). Triethylamine MHz, CDC1) & 195.55, 155.15, 79.32, 46.35, 35.08, 30.57, (2.74 mL, 19.7 mmol) was added, and the solution was 28.38, 2006; IR (thin film) 3350, 2976, 2931, 1686, 1513 cooled to 1° C. utilizing a waterfice bath. Methanesulfonyl cm'. chloride (0.559 mL, 7.22 mmol) was added in portions over 1 hour, and the reaction mixture was stirred overnight. The Example 22: Preparation of (R)-2-((tert-butoxycar reaction mixture was diluted with water, and the layers were bonyl)amino)propyl methanesulfonate (C59) separated. The aqueous layer was extracted with dichlo romethane. The combined extracts were dried over magne 0427 sium sulfate, filtered, and concentrated to provide the title compound as an off-white solid (1.30 g., 78%); H NMR O (400 MHz, CDC1) & 4.91-4.59 (m. 1H), 4.38-4.10 (m, 2H), H V-CH3 3.97 (ddd, J=13.9, 10.1, 5.5 Hz, 1H), 3.04 (s, 3H), 1.45 (s, H3C O N 1& 9H), 1.24 (d. J=6.9 Hz, 3H); 'C NMR (101 MHz, CDC1) & 155.08, 79.79, 72.07, 45.49, 37.27, 28.31, 17.12. D1 1. \, 0429. The following molecules in Table 1 may be pre pared according to the procedures disclosed: P1, P2, P3, P4, P5, P6, P7, P8, P9, P10, and P11 TABLE 1.

tructure and Preparation Method for Prophetic Molecules

No. Structure

P1

P2

P3 US 2017/020880.6 A1 Jul. 27, 2017 42

TABLE 1-continued

Structure and Preparation Method for Prophetic Molecules

No. Structure

P6

US 2017/020880.6 A1 Jul. 27, 2017 67

(R)-2-((2-Aminopropyl)thio)acetonitrile hydrochlo 0726) Isolated as a pale yellow oil (0.562 g, 19%); H ride (C141) NMR (300 MHz, CDC1 & 4.62 (s, 1H), 3.99-3.74 (m, 1H), 0718 2.91 (t, J=14.1 Hz, 2H), 2.82-2.66 (m, 2H), 1.71 (t, J= 18.3 Hz, 3H), 1.45 (s.9H), 1.21 (d. J=6.7 Hz, 3H); 'F NMR (471 MHz, CDC1) 8 -87.83-89.54 (m); 'C NMR (126 MHz, H-Cl CDC1,) & 155.14, 123.89 (t, J=239.8 Hz), 79.45, 45.97, HN 40.09, 39.01 (t, J=29.1 Hz), 28.39, 22.33 (t, J=27.1 Hz), n S 1N 19.95; HRMS-ESI (m/z) M+H" calcd for CHFNOS, CH3 292.1153; found, 292.1152. Example 23: Preparation of 4-vinyl-1-naphthoic 0719. Isolated as a salmon amorphous solid (0.315 g, acid (C145) 78%); H NMR (400 MHz, DMSO-d) & 8.27 (s, 3H), 3.90-3.79 (m, 2H), 3.47-3.35 (m, 1H), 3.00 (dd, J=13.9, 5.9 0727 HZ, 1H), 2.83 (dd, J=13.9, 7.6 Hz, 1H), 1.29 (d. J=6.5 Hz, 3H); IR (thin film) 2841, 2241 cm; HRMS-ESI (m/z) M+H" calcd for CHNS, 131.0637; found, 131.0636. (R)-3-((2-Aminopropyl)thio)propanenitrile hydro chloride (C142) 21 0720 OH

H-Cl HN 2 2 --~1. 0728. To a stirred solution of 4-bromo-1-naphthoic acid CH3 (2.50 g, 9.98 mmol) in dimethyl sulfoxide (32.3 mL) was added potassium vinyltrifluoroborate (1.33 g, 9.96 mmol), 0721) Isolated as an orange oil (0.350 g.90%): 'H NMR potassium carbonate (3.85 g, 27.9 mmol) and 1,1'-bis (400 MHz, CDC1) & 7.88-7.83 (m. 1H), 7.78 (dd, J=8.1, 1.8 (diphenylphosphino) ferrocene-dichloropalladium(II) HZ, 1H), 7.61 (d. J=8.1 Hz, 1H), 7.43 (s. 2H), 5.90-5.74 (m, (0.364 g. 0.498 mmol). The reaction mixture was heated in 2H), 4.60 (p, J=8.8 Hz, 1H), 4.46-4.32 (m, 1H), 2.89-2.68 an 80° C. bath for 18 hours. The reaction mixture was cooled (m, 4H), 2.49-2.34 (m, 2H), 1.35 (d. J=6.7 Hz, 3H); HRMS to ambient temperature and diluted with 1 N aqueous ESI (m/z) M+H" calcd for CHNS, 145.0794: found, hydrochloric acid solution (150 mL) and water (150 mL). 145.0793. The mixture was extracted with ethyl acetate. The organic (R)-1-((3,3,3-Trifluoropropyl)thio)propan-2-amine layer was washed with brine, dried over sodium sulfate and hydrochloride (C143) concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column 0722 chromatography (SiO, eluting with 0-100% ethyl acetate in hexanes) to afford the title compound as a bright yellow solid (1.36 g. 62%); mp 147-155° C.; H NMR (300 MHz, H-Cl F acetone-d) & 11.42 (s, 1H), 9.16-9.03 (m. 1H), 8.31-8.25 HN (m. 2H), 7.77 (dd, J=7.7, 0.7 Hz, 1H), 7.70-7.57 (m, 3H), 5.95 (dd, J=17.2, 1.5 Hz, 1H), 5.62 (dd, J=11.1, 1.5 Hz, 1H): CH^^-s, ESIMS m/z 197 (IM-HI). Example 24: Preparation 0723 Isolated as an orange oil (0.345 g, 89%); H NMR 1-bromo-3-chloro-5-(2.2.2-trifluoroethyl)benzene (400 MHz, DMSO-d) & 8.15 (s, 3H), 3.30-3.19 (m, 1H), (C146) 2.84 (dd, J=13.9, 6.0 Hz, 1H), 2.78-2.52 (m, 5H), 1.26 (d. J=6.5 Hz, 3H); IR (thin film) 2899 cm; HRMS-ESI (m/z) 0729 M+H" calcd for CHFNS, 188.0715; found, 188.0715. C Br 0724. The following compound was prepared in like manner to the procedure outlined in Example 20: tert-Butyl (R)-(1-((2,2-difluoropropyl)thio)propan-2- yl)carbamate (C144) 0725 F F F H H3C O N CH3 0730 (3-Bromo-5-chlorophenyl)boronic acid (4g, 17.00 HC s^X. mmol) was added to a flask with 2.2.2-trifluoroethan-1- CH, O CH3 F F amine hydrochloride (9.22 g, 68.0 mmol), sodium nitrite (5.87 g. 85 mmol), and ammonium chloride (3.64 g. 68.0 mmol). The reaction was heated to 100°C. overnight. At this US 2017/020880.6 A1 Jul. 27, 2017

point, the solvent was removed, and the residue was dis (0735 Isolated as a yellow oil (0.665 g, 62%); H NMR solved in dimethyl sulfoxide (20 mL). Potassium fluoride (400 MHz, CDC1) & 10.01 (s, 1H), 7.96-7.85 (m, 2H), 7.75 (1.976 g. 34.0 mmol) was added, and the mixture was heated (s, 1H), 1.96 (t, J=18.2 Hz, 3H); 'F NMR (376 MHz, to 100° C. for 2 hours. After cooling, the mixture was diluted CDC1,) 8-88.26; IR (thin film) 1705 cm; ESIMS m/z. 205 with water and extracted with dichloromethane. After (IM+H"). extraction and solvent removal, the residue was purified by silica gel chromatography eluting with hexanes. The title 3-Chloro-5-(1,1-difluoropropyl)benzaldehyde compound was recovered as a clear, colorless oil that crystallized upon standing (3.00 g. 64.5%); H NMR (300 (C155) MHz, CDC1) & 7.52 (t, J=1.8 Hz, 1H), 7.35 (s, 1H), 7.24 (s, 0736 1H), 3.32 (q, 1=10.5 Hz, 2H), F NMR (47.1 MHz, CDC1) 8 -65.64. ESIMS m/z 274 (M+H"). Example 25: Preparation H 3-chloro-5-(2.2.2-trifluoroethyl)benzaldehyde C (C147) O 0731

H H3C F F C O (0737. Isolated as a clear yellow oil (0.700 g, 86%); H NMR (400 MHz, CDC1) & 10.01 (s, 1H), 7.92 (d. J=1.7 Hz, 1H), 7.86 (s, 1H), 7.71 (t, J=1.8 Hz, 1H), 2.27-2.06 (m, 2H), F 1.02 (t, J=7.5 Hz, 3H); 'F NMR (376 MHz, CDC1,) & F -97.93: IR (thin film) 1705 cm; EIMS m/z 218 (MI). F 3-Chloro-5-(1,1-difluorobutyl)benzaldehyde (C156) 0732 1-Bromo-3-chloro-5-(2.2.2-trifluoroethyl)benzene 0738 (C146) (2 g, 7.31 mmol) was dissolved in tetrahydrofuran at 0° C., and isopropylmagnesium chloride-lithium chloride complex (1.3 M solution in tetrahydrofuran; 6.75 mL, 8.78 mmol) was added dropwise. The reaction mixture was stirred for 4 hours with warming to room temperature, and C N,N-dimethylformamide (0.680 mL, 8.78 mmol) was added dropwise. The reaction mixture was stirred for 30 minutes, then 1 N aqueous hydrochloric acid was added, and the mixture was extracted with diethyl ether. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to a yellow oil. Purification by silica gel chromatography eluting 0-20% acetone in hexanes gave the title compound as a pale yellow oil (1.33 g, 82%): H NMR (400 MHz, CDC1) & 9.98 (s, 1H), 7.90-7.78 (m, (0739 Isolated as a clear yellow oil (0.690 g, 89%); H 1H), 7.71 (s, 1H), 7.56 (s, 1H), 3.45 (q, J=10.5 Hz, 2H); 'F NMR (400 MHz, CDC1) & 10.01 (s, 1H), 7.91 (d. J=1.5 Hz, NMR (376 MHz, CDC1) 8 -65.67; IR (thin film) 1704 1H), 7.86 (s, 1H), 7.71 (d. J=1.6 Hz, 1H), 2.20-2.03 (m, 2H), cm': EIMS m/z 221 (MI). 1.53-141 (m, 2H), 0.96 (t, J=7.4 Hz, 3H); 'F NMR (376 0733. The following compounds were prepared in like MHz, CDC1,) 8 -95.90; IR (thin film) 1704 cm': EIMS m/z manner to the procedure outlined in Example 25: 232 (MI"). 3-Chloro-5-(1,1-difluoroethyl)benzaldehyde (C154) Example 26: Preparation of 0734 1-(3-bromo-5-chlorophenyl)ethan-1-one (C148) 0740

C CH

Br US 2017/020880.6 A1 Jul. 27, 2017 69

0741) 1,3-Dibromo-5-chlorobenzene (5.0 g, 18.5 mmol) Example 27: Preparation of was dissolved in diethyl ether (61.6 mL) and cooled to -78° 1-bromo-3-chloro-5-(1,1-difluoroethyl)benzene C. Because the compound came out of solution, the mixture (C151) was removed from the cooling bath. As soon as stirring was again visible from temperature warming, n-butyllithium 0747 (8.14 mL. 20.34 mmol) was added dropwise, and the solu tion was re-immersed in the cold bath. The solution took on a bright yellow color, and the mixture was stirred for 30 C Br minutes. At this point a slight yellow precipitate was visible. N-Methoxy-N-methylacetamide (2.359 mL, 22.19 mmol) was added dropwise, and the reaction mixture was stirred for 10 minutes, then warmed slowly to room temperature. The reaction mixture was quenched with 1 N hydrochloric acid F and was extracted with diethyl ether. The combined organic HC F extracts were washed with brine, dried over sodium sulfate and concentrated. The resulting oil was purified on silica running a 0-15% gradient of acetone in hexanes. The title 07:48 1-(3-Bromo-5-chlorophenyl)ethan-1-one (C148) compound was isolated as a white solid (3.7 g, 86%); mp (1.6 g. 6.85 mmol) was dissolved in dichloromethane (34.3 33-36° C.; H NMR (300 MHz, CDC1) & 7.97-7.95 (m, 1H), mL) to which were added sequentially Deoxo-Fluor R. (bis 7.85 (dd, J=1.5 Hz, 1H), 7.71 (t, J=1.8 Hz, 1H), 2.59 (s.3H): (2-methoxyethyl)aminosulfur trifluoride; 4.42 mL, 10.28 IR (thin film) 1687 cm; ESIMS m/z 233 (M+H"). mmol) and one drop of methanol. The reaction mixture was 0742 The following compounds were prepared in like stirred at room temperature overnight. An additional 1.5 equivalents of Deoxo-Fluor R were added, and the reaction manner to the procedure outlined in Example 26: mixture was heated to 40° C. for 24 hours. The reaction 1-(3-Bromo-5-chlorophenyl)propan-1-one (C149) mixture was concentrated under light vacuum (300 mbar) to remove the dichloromethane and was heated to 70° C. for 3 0743 hours. The reaction was quenched by slow addition of saturated aqueous Sodium bicarbonate Solution with stirring. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with brine, dried over sodium sulfate, C CH3 and concentrated. Purification by silica gel chromatography eluting with hexanes provided the title compound as a clear, colorless oil (1.34g, 77%); H NMR (400 MHz, CDC1) & 7.57 (d. J=1.7 Hz, 1H), 7.53 (s, 1H), 7.43 (s, 1H), 1.89 (t, Br J=18.2 Hz, 3H); 'F NMR (376 MHz, CDC1,) & -88.39; ESIMS m/z 255 (IM+H"). 0744) Isolated as a white solid (1.71 g, 62%); H NMR 0749. The following compounds were prepared in like (400 MHz, CDC1) & 7.96 (t, J=1.6 Hz, 1H), 7.90-7.81 (m, manner to the procedure outlined in Example 27: 1H), 7.69 (t, J=1.8 Hz, 1H), 2.96 (q, J=7.2 Hz, 2H), 1.22 (t, J=7.2 Hz, 3H); 'C NMR (101 MHz, CDC1,) & 198.01, 1-Bromo-3-chloro-5-(1,1-difluoropropyl)benzene 139.51,135.78, 135.33, 129.38, 126.91, 123.25, 32.06, 7.98: (C152) ESIMS m/z 248 (IM+H"). 0750 1-(3-Bromo-5-chlorophenyl)butan-1-one (C150) 0745 CH F F

C CH3

C Br

Br

0746 Isolated as clear colorless oil (1.65 g, 57%): 'H NMR (400 MHz, CDC1) & 7.95 (t, J=1.6 Hz, 1H), 7.84 (t, J=1.7 Hz, 1H), 7.69 (t, J=1.8 Hz, 1H), 2.90 (t, J–7.2 Hz, 2H), (0751) Isolated as a clear yellow oil (1.00 g, 83%): 'H 1.76 (h, J=7.4 Hz, 2H), 1.00 (t, J=7.4 Hz, 3H); 'C NMR NMR (400 MHz, CDC1) & 7.57 (t, J=1.8 Hz, 1H), 7.50 (s, (101 MHz, CDC1) & 197.53, 139.67, 135.75, 135.28, 129. 1H), 7.39 (s, 1H), 2.11 (, J=23.7, 16.2, 7.5 Hz, 2H), 0.99 40, 126.93, 123.22, 40.61, 1747, 13.72; IR (thin film) 1693, (t, J–7.5 Hz, 3H); F NMR (376 MHz, CDC1) 8 -97.97; 1559, 1203 cm; ESIMS m/z 262 (IM+H"). IR (thin film) 1566 cm: ESIMS m/z 268 (M+H"). US 2017/020880.6 A1 Jul. 27, 2017 70

1-Bromo-3-chloro-5-(1,-difluorobutyl)benzene 0756. The following compounds were prepared in like (C153) manner to the procedure outlined in Example 29: 0752 (Z) N-(2-(Methylthio)propyl)-4-(1,4,4,4-tetra fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2- (trifluoromethyl)benzamide (F89) C Br 0757

F H3C F

(0753) Isolated as a clear yellow oil (0.940 g, 96%): 'H NMR (400 MHz, CDC1) & 7.57 (t, J=1.8 Hz, 1H), 7.49 (s. 1H), 7.39 (s, 1H), 2.14-1.98 (m, 2H), 1.51-1.39 (m, 2H), 0758 Isolated as a yellow glass (0.20 g, 34%). 0.95 (t, J–74 Hz, 3H); F NMR (376 MHz, CDC1,) & H).-95.94: IR (thin film) 1565 cm:Cm , ESIMS m/zZ 282 (IM(M+ N—((R)-1-((2-Fluoroethyl)thio)propan-2-yl)-4-((Z)- 14,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1- en-1-yl)-2-(trifluoromethyl)benzamide (F84) Example 29: Preparation of (Z)-4-(1,4,4,4-tetra fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2- 0759) (trifluoromethyl)-N-(2-((trifluoromethyl)thio)ethyl)

benzamide (F92) 0754)

0760. Isolated as a pale yellow glass (0.273 g, 35%). (Z) N-(2-((2-Fluoroethyl)thio)ethyl)-4-(1.4.4.4- tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)- 0755 (Z)-4-(1,4,4,4-Tetrafluoro-3-(3,4,5-trichlorophe 2-(trifluoromethyl)benzamide (F125) nyl) but-1-en-1-yl)-2-(trifluoromethyl)benzoyl chloride (C23) (1.0 mL, 0.45 M, 0.45 mmol) in dichloromethane was 0761 added to a colorless solution of 2-((trifluoromethyl)thio) ethan-1-amine (100 mg, 0.689 mmol) and 4-methylmorpho line (0.148 mL, 1.350 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was agitated for two hours. The reaction mixture was diluted with ethyl acetate and 5% aqueous citric acid, and the layers were separated. The organic solution was washed with water, dried with magne sium sulfate, filtered, and concentrated. The resulting resi due was purified by chromatography on SiO2 with a linear gradient of 0-50% ethyl acetate in hexanes providing the title compound as a yellow oil (0.204 g. 69%). 0762. Isolated as a colorless oil (0.249 g, 34%). US 2017/020880.6 A1 Jul. 27, 2017

N—((R)-1-((2,2-Difluoropropyl)thio)propan-2-yl)-4- organic solution was washed with 5% citric acid, water, and ((Z)-1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but brine, dried with sodium sulfate, filtered, and concentrated. 1-en-1-yl)-2-(trifluoromethyl)benzamide (F113) The resulting residue was purified by flash silica chroma 0763 tography. The title compound was isolated as a yellow glass (0.37 g. 69%). Example 31: Preparation of tert-butyl (R)-(1-((2- fluoroethyl)thio)propan-2-yl)carbamate (C157) 0769 F CH H S^s-nkCH F HC O N F 3 S 1N1 H3C 0764) Isolated as a yellow foam (0.300 g, 45%). CH, O CH3 (Z) N-(2-Methyl-1-(methylsulfonyl)propan-2-yl)- 4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1- en-1-yl)-2-(trifluoromethyl)benzamide (F100) 0765 (0770 Aqueous sodium hydroxide (2.0 M, 8.5 mL, 17

mmol) was added to a solution of (R)—S-(2-((tert-butoxy carbonyl)amino)propyl) ethanethioate (C58) (2.0 g, 8.5 mmol) in isopropanol at 0° C. After stirring 2 hours, 1-fluoro-2-iodoethane (1.76 g, 10.1 mmol) was added and the reaction mixture was left to stir overnight. The reaction mixture was partioned between ethyl acetate and water. The organics were separated, washed with Saturated sodium bicarbonate and brine, dried with magnesium sulfate, and concentrated. The resulting residue was purified by flash silica chromatography. The title compound was isolated as a 0766 Isolated as a yellow foam (0.089 g, 23%) using pale yellow liquid (1.55 g 72%); H NMR (500 MHz, diisopropylethyl amine in place of N-methyl morpholine. DMSO-d) & 6.80 (d. J=8.2 Hz, 1H), 4.53 (dt, J–47.3, 6.4 Hz, 2H), 3.54 (h, J=6.9 HZ, 1H), 2.81 (dt, J=21.2, 6.4 Hz, Example 30: Preparation of (Z) N-(3-(methylthio) 2H), 2.63-2.51 (m, 2H), 1.38 (s, 9H), 1.07 (d. J=6.7 Hz, 3H): butan-2-yl)-4-(1,4,4,4-tetrafluoro-3-(3,4,5-trichloro 'F NMR (471 MHz, DMSO-d) & -211.55 (tt, J=46.9, 21.3 phenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamide Hz); 'C NMR (126 MHz, DMSO-d) & 155.41, 83.20 (d. (F101) J=167.3 Hz), 78.02, 46.51, 38.34, 31.84 (d. J–20.5 Hz), 2872, 20.19; IR (thin film) 3340, 2975, 2931, 1687, 1504 0767 C . 0771. The following compounds were prepared in like manner to the procedure outlined in Example 31: tert-Butyl (R)-(1-((2,2-difluoroethyl)thio)propan-2- yl)carbamate (C158) 0772

H H3C O N F S 0768 2-(3H-1.2.3Triazolo 4,5-b]pyridin-3-yl)-1,1,3,3- H3C tetramethylisouronium hexafluorophosphate(V) (460 mg. CH, O CH3 F 1.211 mmol) was added to an orange solution of (Z)-4-(1, 4,4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2- (trifluoromethyl)benzoic acid (C2) (400 mg. 0.807 mmol), (0773) Isolated as a pale yellow oil (0.323 g, 39%); H N-ethyl-N-isopropylpropan-2-amine (324 uL, 1.856 mmol), NMR (400 MHz, CDC1,) & 5.89 (tt, J=56.5, 4.5 Hz, 1H), and 3-(methylthio)butan-2-amine (115 mg, 0.969 mmol) in 4.54 (s, 1H), 3.84 (s, 1H), 2.89 (tdd, J=15.4, 4.5, 1.4 Hz, 2H), N,N-dimethylformamide (2.7 mL). The reaction mixture 2.79-2.62 (m, 2H), 1.45 (s, 10H), 1.21 (d. J=6.7 Hz, 3H); IR was stirred overnight at room temperature. The reaction (thin film) 1688 cm; HRMS-ESI (m/z) M+Na" calcd for mixture was diluted with water and ethyl acetate. The CHFNOS, 278.0997; found, 278.1009.

US 2017/020880.6 A1 Jul. 27, 2017

IR (thin film) 3339, 2976, 2931, 1688, 1502 cm; HRMS filtered, and concentrated. Purification by flash column ESI (m/z) M+Na" calcd for CHFNOS, 304.1153; chromatography using 40% ethyl acetate in hexanes pro found, 3.04.1150. vided the title compound as a pale yellow gum (0.055 g, 65%); H NMR (400 MHz, CDC1) & 10.47 (d. J=1.2 Hz, Example 32: Preparation of tert-butyl (2-((2-fluoro 1H), 7.92-7.80 (m, 2H), 7.75 (dd, J=8.8, 1.6 Hz, 2H), 7.61 ethyl)thio)ethyl)carbamate (C166) (d. J=8.0 Hz, 1H), 6.39 (dd, J=8.1, 3.0 Hz, 1H), 6.04-5.79 0788 (m. 1H), 4.79-4.62 (m, 2H), 4.17-4.03 (m, 1H), 3.96 (dt, J=15.5, 9.3 Hz, 1H), 3.54 (dd, J=14.5, 6.6 Hz, 1H), 3.40 (dd, J=14.5, 5.0 Hz, 1H), 1.52 (d. J=6.9 Hz, 3H); 'F NMR (376 MHz, CDC1) & -59.11 (d. J=2.4 Hz), -61.14, -67.67, >''N-> 1n -107.51; ESIMS m/z 674 (IM-HI). CH, O Example 34: Preparation of 4-((Z)-3-(3,4-dichloro 5-(difluoromethyl)phenyl)-1,4,4,4-tetrafluorobut-1- 0789 Sodium hydride (60% dispersion in paraffin, 1.0 g, en-1-yl)-N-((R)-1-((2.2.2-trifluoroethyl)sulfonyl) 25 mmol) was added to tert-butyl (2-mercaptoethyl)carbam propan-2-yl)-2-(trifluoromethyl)benzamide (F70) ate (4.0 g, 22.6 mmol) in N,N-dimethylformamide (59.8 mL) at 0°C. After stirring 20 minutes, 1-fluoro-2-iodoethane 0792 (2.6 g. 15.0 mmol) was added and the reaction mixture was left to stir overnight. The reaction mixture was diluted with water and extracted with diethyl ether (2x). The organic layer was washed with water and brine, dried with magne sium sulfate, filtered, and concentrated. The resulting liquid was purified by flash silica chromatography. The title com pound was isolated as a colorless liquid (1.5 g, 43%); H NMR (500 MHz, DMSO-d) & 6.98-6.86 (m. 1H), 4.53 (dt, J=47.3, 6.3 Hz, 2H), 3.08 (dt, J=7.6, 6.1 Hz, 2H), 2.81 (dt, J=21.7, 6.3 Hz, 2H), 2.57 (dd, J=7.9, 6.4 Hz, 2H), 1.38 (s, 9H); 'C NMR (126 MHz, DMSO-d) & 155.96, 83.26 (d. J=167.6 Hz), 78.17, 40.40, 31.66, 31.27 (d. J=20.7 Hz), 28.69; F NMR (471 MHz, DMSO-d) & -211.77 (tt, 0793 Bis(2-methoxyethyl)aminosulfur trifluoride (114 J=47.3, 21.7 Hz); IR (thin film) 1689 cm; HRMS-ESI mg, 0.517 mmol) was added to a solution of 4-((Z)-3-(3,4- (m/z) M+Na" calcd for C.H.FNOS, 246.0934; found, dichloro-5-formylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)- 246.0937. N—((R)-1-((2, 2.2-trifluoroethyl)sulfonyl)propan-2-yl)-2- (trifluoromethyl)benzamide (C167) (0.07 g., 0.103 mmol) in Example 33: Preparation of 4-((Z)-3-(3,4-dichloro dichloromethane (0.5 mL) at room temperature. One drop of 5-formylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)- methanol was added and the reaction mixture was stirred at N—((R)-1-((2.2.2-trifluoroethyl)sulfonyl)propan-2- 20° C. for 12 hours. The reaction mixture was quenched with yl)-2-(trifluoromethyl)benzamide (C167) water (5 mL) and then extracted with ethyl acetate (15 mL). The organic layer was dried over sodium sulfate, filtered, 0790 and concentrated. Purification by flash column chromatog raphy using 35% ethyl acetate in hexanes provided the title compound as a white wax (0.030 g., 38%). Example 35: Separation of 4-((R.Z)-1,4,4,4-tetra fluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-N- ((R)-1-((2.2.2-trifluoroethyl)sulfonyl)propan-2-yl)-2- (trifluoromethyl)benzamide (F72) and 4-((S.Z)-1,4, 4,4-tetrafluoro-3-(3,4,5-trichlorophenyl)but-1-en-1- yl)-N-((R)-1-((2.2.2-trifluoroethyl)sulfonyl) propan-2-yl)-2-(trifluoromethyl)benzamide (F136) 0791 Osmium tetroxide (2.5% in tert-butanol, 60 mg. 0.006 mmol) was added to a solution of 4-((Z)-3-(3,4- 0794. The title molecules were prepared as as a mixture dichloro-5-vinylphenyl)-1,4,4,4-tetrafluorobut-1-en-1-yl)- as described in Example 15. The diastereomeric pairs were N—((R)-1-((2.2.2-trifluoroethyl)sulfonyl)propan-2-yl)-2- separated by Supercritical fluid (SCF) chromatography using (trifluoromethyl)benzamide (F73) (0.08 g., 0.12 mmol) in Chiralpak AD-H (250x21 mm), 5L column using methanol tetrahydrofuran-water (2:1, 1.0 mL) at room temperature. as the mobile phase (isocratic 70:30, CO, and methanol The reaction mixture was stirred for 5 minutes. Sodium respectively) with a flow rate of 60 g/min at ambient periodate (0.076 g., 0.356 mmol) was added to the reaction temperature. Diastereomer F72 was collected at a retention mixture. The reaction mixture was stirred at 20° C. for 12 time of 1.78 minutes and possessed an optical rotation of hours. The reaction mixture was quenched with sodium C-+41.8 (c. 0.29% in MeOH). Diastereomer F136 was bisulfate (100 mg) and then extracted with ethyl acetate (10 collected at 2.60 minutes and possessed an optical rotation mL). The organic layer was dried over sodium sulfate, of C.I-73.3 (c. 0.28% in MeOH). US 2017/020880.6 A1 Jul. 27, 2017 74

Example 37: Preparation of 3,5-dichloro-4-(difluoromethyl)benzaldehyde (C169) 0799

C

C

0795 F72 was isolated as an off-white solid. 0800 To a stirred solution of methyl 3,5-dichloro-4- (difluoromethyl)benzoate (C170) (5.00 g, 19.6 mmol) in methylene chloride (20 mL) cooled in a -78° C. bath was added dropwise diisobutylaluminum hydride (1 M in THF: 39.2 mL, 39.2 mmol). After 2 hours, the reaction mixture F was treated with cold water and extracted with methylene F chloride. The organic layer was washed with brine, dried H over sodium Sulfate and concentrated under reduced pres N wCH3 sure to afford crude compound. Purification by column enantiomerically pure chromatography (SiO, 100-200 mesh, eluting with 5% O n F ethyl acetate in petroleum ether) afforded the title compound syg as a pale brown solid (3.0 g. 66%): 'H NMR (400 MHz, 4. \, F F DMSO-d) & 10.00 (s, 1H), 8.05 (s. 2H), 7.52 (t, J=52.0 Hz, 1H); IR (thin film) 1709, 1362, 1057 cm; EIMS m/z 224 (IMI). Example 38: Preparation of methyl 3,5-dichloro-4-(difluoromethyl)benzoate (C170) 0796 F136 was isolated as an off-white solid. 0801) Example 36: Preparation of 3-chloro-4,5-difluorobenzaldehyde (C168) HC 3 No

0797 C O

F

C F C

0802 Bis(2-methoxyethyl)aminosulfur trifluoride (1.93 0798. To a stirred solution of methyl (3-chloro-4,5-dif g, 8.80 mmol) was added to a solution methyl 3,5-dichloro luorophenyl)methanol (4.00 g, 22.4 mmol) in methylene 4-formylbenzoate (1.00 g, 4.29 mmol) in dichloromethane chloride (150 mL) was added manganese dioxide (15.0 g, (10 mL) at room temperature. One drop of methanol was 179 mmol). After stirring for 12 hours at room temperature, added and the reaction mixture was stirred at 20° C. for 12 the reaction mixture was filtered through Celite(R). The hours. The reaction mixture was quenched with water (100 mL) and then extracted with ethyl acetate (300 mL). The filtrate was concentrated under reduced pressure to afford organic layer was dried over Sodium sulfate, filtered, and the title compound as a colorless oil (3.5g, 86%); H NMR concentrated. Purification by flash column chromatography (300 MHz, CDC1) & 9.89 (s, 1H), 7.77-7.74 (m. 1H), provided the title compound as a pale yellow solid (0.70 g, 7.66-7.61 (m, 1H); IR (thin film) 3302, 1709, 750 cm; 63%): 'H NMR (300 MHz, DMSO-d) & 8.02 (s. 2H), 7.50 EIMS m/z. 176 (MI"). (t, J=52.2 Hz, 1H), 3.99 (s.3H); EIMS m/z 254 (M'.). US 2017/020880.6 A1 Jul. 27, 2017 75

Example 39: Preparation of 1-(3,4-dichloro-5-meth in large Swarms causing devastating crop losses. It is known ylphenyl)-2.2.2-trifluoroethan-1-one (C173) to be resistant to several pesticides. 0807 Cabbage Looper is a serious pest found throughout 0803 the world. It attacks alfalfa, beans, beets, broccoli, Brussel sprouts, cabbage, cantaloupe, cauliflower, celery, collards, F cotton, cucumbers, eggplant, kale, lettuce, melons, mustard, F F parsley, , peppers, potatoes, soybeans, spinach, Squash, tomatoes, turnips, and watermelons, among other crops. C This species is very destructive to plants due to its Voracious O appetite. The larvae consume three times their weight in food daily. The feeding sites are marked by large accumu lations of sticky, wet, fecal material. It is known to be C resistant to several pesticides. CH 0808 Corn earworm is considered by some to be the most costly crop pest in North America. It often attacks valuable crops, and the harvested portion of the crop. This 0804) To 5-bromo-1,2-dichloro-3-methylbenzene (6.9 g, pest damages alfalfa, artichoke, asparagus, cabbage, canta 29 mmol) in tetrahydrofuran (65 mL) cooled in an ice bath loupe, collard, corn, cotton, cowpea, cucumber, eggplant, under nitrogen was added isopropylmagnesium chloride lettuce, lima bean, melon, okra, , pepper, potato, pump lithium chloride complex in tetrahydrofuran (26.8 mL, 34.8 kin, Snap bean, Soybean, spinach, Squash, Sugarcane, Sweet mmol). After 1 hour methyl 2.2.2-trifluoroacetate (3.79 mL, potato, tomato, and watermelon, among other crops. Fur 37.7 mmol) was added. After 30 minutes, the ice bath was thermore, this pest is also known to be resistant to certain removed, and the solution was stirred for 1 hour. The insecticides. reaction mixture was quenched with aqueous hydrochloric acid (2 N). The mixture was concentrated and extracted with 0809 Consequently, because of the above factors control dichloromethane. The organic layer was washed with brine, of these pests is important. Furthermore, molecules that dried over sodium sulfate, filtered, and concentrated. Puri control these pests (BAW, CEW, and CL), which are known fication by column chromatography (SiO, petroleum ether) as chewing pests, are useful in controlling other pests that provided the title compound as a white solid (5.9 g, 80%): chew on plants. H NMR (400 MHz, CDC1) & 8.00 (s, 1H), & 7.83 (s, 1H), 0810 Certain molecules disclosed in this document were 2.51 (s, 3H): EIMS m/z 256 (MI"). tested against BAW, CEW, and CL using procedures described in the following examples. In the reporting of the Biological Assays results, the “BAW, CEW, & CL Rating Table” was used (See Table Section). 0805. The following bioassays against Beet Armyworm (Spodoptera exigua), Cabbage Looper (Trichoplusia ni), Bioassays on BAW Corn Earworm (Helicoverpa zea), Green Peach Aphid (Myzus persicae), and Yellow Fever Mosquito (Aedes 0811 Bioassays on BAW were conducted using a 128 aegypti), are included herein due to the damage they inflict. well diet tray assay. One to five second instar BAW larvae Furthermore, the Beet Armyworm, Corn Earworm, and were placed in each well (3 mL) of the diet tray that had been Cabbage Looper are three good indicator species for a broad previously filled with 1 mL of artificial diet to which 50 range of chewing pests. Additionally, the Green Peach Aphid ug/cm of the test molecule (dissolved in 50 uL of 90:10 is a good indicator species for a broad range of Sap-feeding acetone-water mixture) had been applied (to each of eight pests. The results with these four indicator species along wells) and then allowed to dry. Trays were covered with a with the Yellow Fever Mosquito show the broad usefulness clear self-adhesive cover and held at 25°C., 14:10 light-dark of the molecules of Formula One in controlling pests in for five to seven days. Percent mortality was recorded for the Phyla Arthropoda, Mollusca, and Nematoda (For further larvae in each well; activity in the eight wells was then information see Methods for the Design and Optimization of averaged. The results are indicated in the table entitled New Active Ingredients, Modern Methods in Crop Protec “Table ABC: Biological Results” (See Table Section). tion Research, Edited by Jeschke, P. Kramer, W., Schirmer, U., and Matthias W., p. 1-20, 2012). Bioassays on CL Example A: Bioassays on Beet Armyworm 0812 Bioassays on CL were conducted using a 128-well (Spodoptera Exigua, LAPHEG) (“BAW), Corn diet tray assay. One to five second instar CL larvae were Earworm (Helicoverpa zea, HELIZE) (“CEW), placed in each well (3 mL) of the diet tray that had been and Cabbage Looper (Trichoplusia ni, TRIPNI) previously filled with 1 mL of artificial diet to which 50 (“CL) ug/cm of the test molecule (dissolved in 50 uL of 90:10 acetone-water mixture) had been applied (to each of eight 0806 Beet army worm is a serious pest of economic wells) and then allowed to dry. Trays were covered with a concern for alfalfa, asparagus, beets, citrus, corn, cotton, clear self-adhesive cover and held at 25°C., 14:10 light-dark onions, peas, peppers, potatoes, soybeans, Sugar beets, Sun for five to seven days. Percent mortality was recorded for the flowers, tobacco, tomatoes, among other crops. It is native to larvae in each well; activity in the eight wells was then Southeast Asia but is now found in Africa, Australia, Japan, averaged. The results are indicated in the table entitled North America, and Southern Europe. The larvae may feed “Table ABC: Biological Results” (See Table Section). US 2017/020880.6 A1 Jul. 27, 2017 76

Example B: Bioassays on Green Peach Aphid persons without treatment will die from yellow fever. There (Myzus Persicae, MYZUPE) (“GPA) are an estimated 200,000 cases of yellow fever, causing 30,000 deaths, worldwide each year. Dengue fever is a nasty, 0813 GPA is the most significant aphid pest of peach viral disease; it is sometimes called “breakbone fever” or trees, causing decreased growth, shriveling of the leaves, “break-heart fever because of the intense pain it can pro and the death of various tissues. It is also hazardous because duce. Dengue fever kills about 20,000 people annually. it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the Consequently, because of the above factors control of this nightshade/potato family Solanaceae, and various mosaic pest is important. Furthermore, molecules that control this viruses to many other food crops. GPA attacks Such plants as pest (YFM), which is known as a Sucking pest, are useful in broccoli, burdock, cabbage, carrot, cauliflower, daikon, egg controlling other pests that cause human and animal Suffer plant, green beans, lettuce, macadamia, papaya, peppers, 1ng. Sweet potatoes, tomatoes, watercress, and Zucchini, among 0821 Certain molecules disclosed in this document were other crops. GPA also attacks many ornamental crops such tested against YFM using procedures described in the fol as carnation, chrysanthemum, flowering white cabbage, lowing paragraph. In the reporting of the results, the “GPA poinsettia, and roses. GPA has developed resistance to many & YFM Rating Table” was used (See Table Section). pesticides. Consequently, because of the above factors con 0822 Master plates containing 400 g of a molecule trol of this pest is important. Furthermore, molecules that dissolved in 100 uL of dimethyl sulfoxide (DMSO) (equiva control this pest (GPA), which is known as a sap-feeding lent to a 4000 ppm solution) are used. A master plate of pest, are useful in controlling other pests that feed on the sap assembled molecules contains 15 u per well. To this plate, from plants. 135 uL of a 90:10 water:acetone mixture is added to each 0814 Certain molecules disclosed in this document were well. A robot (BiomekR NXP Laboratory Automation Work tested against GPA using procedures described in the fol station) is programmed to dispense 15 uL aspirations from lowing example. In the reporting of the results, the “GPA & the master plate into an empty 96-well shallow plate YFM Rating Table” was used (See Table Section). (“daughter plate). There are 6 reps (“daughter plates) 0815 Cabbage seedlings grown in 3-inch pots, with 2-3 created per master. The created daughter plates are then small (3-5 cm) true leaves, were used as test substrate. The immediately infested with YFM larvae. seedlings were infested with 20-50 GPA (wingless adult and 0823. The day before plates are to be treated, mosquito nymph stages) one day prior to chemical application. Four eggs are placed in Millipore water containing liver powder pots with individual seedlings were used for each treatment. to begin hatching (4 g. into 400 mL). After the daughter Test molecules (2 mg) were dissolved in 2 mL of acetone/ plates are created using the robot, they are infested with 220 methanol (1:1) solvent, forming stock solutions of 1000 ppm uL of the liver powder/larval mosquito mixture (about 1 test molecule. The stock solutions were diluted 5x with day-old larvae). After plates are infested with mosquito 0.025% Tween 20 in water to obtain the solution at 200 ppm larvae, a non-evaporative lid is used to cover the plate to test molecule. A hand-held aspirator-type sprayer was used reduce drying. Plates are held at room temperature for 3 days for spraying a solution to both sides of cabbage leaves until prior to grading. After 3 days, each well is observed and runoff. Reference plants (solvent check) were sprayed with scored based on mortality. The results are indicated in the the diluent only containing 20% by volume of acetone/ table entitled “Table ABC: Biological Results” (See Table methanol (1:1) solvent. Treated plants were held in a holding Section). room for three days at approximately 25° C. and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant Agriculturally Acceptable Acid Addition Salts, Salt under a microscope. Percent Control was measured by using Derivatives, Solvates, Ester Derivatives, Polymorphs, Abbott’s correction formula (W. S. Abbott, “A Method of Isotopes, and Radionuclides Computing the Effectiveness of an Insecticide” J. Econ. 0824 Molecules of Formula One may be formulated into Entomol. 18 (1925), pp. 265-267) as follows. agriculturally acceptable acid addition salts. By way of a Corrected 96 Control=100*(X-Y)/X non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, Sulfuric, phosphoric, acetic, 0816 where benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, 0817 X=No. of live aphids on solvent check plants Succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, and benzenesulfonic, methanesulfonic, ethanesulfonic, 08.18 Y-No. of live aphids on treated plants hydroxyl-methanesulfonic, and hydroxyethanesulfonic 0819. The results are indicated in the table entitled “Table acids. Additionally, by way of a non-limiting example, an ABC: Biological Results” (See Table Section). acid function can form salts including those derived from alkali or alkaline earth metals and those derived from Example C: Bioassays on Yellow Fever Mosqurro ammonia and amines. Examples of preferred cations include (Aedes aegypti, AEDSAE) (“YFM”) Sodium, potassium, and magnesium. 0820 YEM prefers to feed on humans during the daytime 0825 Molecules of Formula One may be formulated into and is most frequently found in or near human habitations. salt derivatives. By way of a non-limiting example, a salt YFM is a vector for transmitting several diseases. It is a derivative may be prepared by contacting a free base with a mosquito that can spread the dengue fever and yellow fever sufficient amount of the desired acid to produce a salt. A free viruses. Yellow fever is the second most dangerous mos base may be regenerated by treating the salt with a suitable quito-borne disease after malaria. Yellow fever is an acute dilute aqueous base solution Such as dilute aqueous Sodium viral hemorrhagic disease and up to 50% of severely affected hydroxide, potassium carbonate, ammonia, and Sodium US 2017/020880.6 A1 Jul. 27, 2017 77 bicarbonate. As an example, in many cases, a pesticide. Such 0833. In another embodiment, molecules of Formula One as 2,4-D, is made more water-soluble by converting it to its may be used in combination (Such as, in a compositional dimethylamine salt. mixture, or a simultaneous or sequential application) with 0826 Molecules of Formula One may be formulated into one or more molecules having acaricidal, algicidal, avicidal, stable complexes with a solvent, such that the complex bactericidal, fungicidal, herbicidal, insecticidal, mollusci remains intact after the non-complexed solvent is removed. cidal, nematicidal, rodenticidal, and/or virucidal properties. These complexes are often referred to as “solvates.” How 0834. In another embodiment, the molecules of Formula ever, it is particularly desirable to form stable hydrates with One may be used in combination (such as, in a composi water as the solvent. tional mixture, or a simultaneous or sequential application) 0827. Molecules of Formula One may be made into ester with one or more molecules that are antifeedants, bird derivatives. These ester derivatives can then be applied in repellents, chemosterilants, herbicide Safeners, insect attrac the same manner as the molecules disclosed in this docu tants, insect repellents, mammal repellents, mating disrupt ment is applied. ers, plant activators, plant growth regulators, and/or syner gists. 0828 Molecules of Formula One may be made as various crystal polymorphs. Polymorphism is important in the 0835. In another embodiment, molecules of Formula One development of agrochemicals since different crystal poly may also be used in combination (such as in a compositional morphs or structures of the same molecule can have vastly mixture, or a simultaneous or sequential application) with different physical properties and biological performances. one or more biopesticides. 0829. Molecules of Formula One may be made with 0836. In another embodiment, in a pesticidal composition different isotopes. Of particular importance are molecules combinations of a molecule of Formula One and an active having H (also known as deuterium) or H (also known as ingredient may be used in a wide variety of weight ratios. tritium) in place of 1H. Molecules of Formula One may be For example, in a two component mixture, the weight ratio made with different radionuclides. Of particular importance of a molecule of Formula One to an active ingredient, may are molecules having C. Molecules of Formula One hav be from about 100:1 to about 1:100; in another example the ing deuterium, tritium, or 'C may be used in biological weight ratio may be about 50:1 to about 1:50; in another studies allowing tracing in chemical and physiological pro example the weight ratio may be about 20:1 to about 1:20; cesses and half-life studies, as well as, MoA studies. in another example the weight ratio may be about 10:1 to about 1:10; in another example the weight ratio may be Stereoisomers about 5:1 to 1:5; in another example the weight ratio may be about 3:1 to about 1:3; in another example the weight ratio 0830 Molecules of Formula One may exist as one or may be about 2:1 to about 1:2; and in a final example the more stereoisomers. Thus, certain molecules may be pro weight ratio may be about 1:1 (See Table B). However, in duced as racemic mixtures. It will be appreciated by those general, weight ratios less than about 10:1 to about 1:10 are skilled in the art that one stereoisomer may be more active than the other Stereoisomers. Individual stereoisomers may preferred. It is also preferred sometimes to use a three or four be obtained by known selective synthetic procedures, by component mixture comprising a molecule of Formula One conventional synthetic procedures using resolved starting and one or more active ingredients. materials, or by conventional resolution procedures. Certain molecules disclosed in this document can exist as two or TABLE B more isomers. The various isomers include geometric iso mers, diastereomers, and enantiomers. Thus, the molecules Weight Ratios disclosed in this document include geometric isomers, race Molecule of the Formula One:active ingredient mic mixtures, individual stereoisomers, and optically active 100:1 to 1:100 mixtures. It will be appreciated by those skilled in the art that SO:1 to 1:SO one isomer may be more active than the others. The struc 20:1 to 1:20 tures disclosed in the present disclosure are drawn in only 10:1 to 1:10 one geometric form for clarity, but are intended to represent 5:1 to 1:5 all geometric forms of the molecule. 3:1 to 1:3 2:1 to 1:2 Combinations 1:1 0831. In another embodiment of this invention, mol ecules of Formula One may be used in combination (such as, 0837 Weight ratios of a molecule of Formula One to an in a compositional mixture, or a simultaneous or sequential active ingredient may also be depicted as X:Y; wherein X is application) with one or more active ingredients. the parts by weight of a molecule of Formula One and Y is 0832. In another embodiment of this invention, mol the parts by weight of active ingredient. The numerical range ecules of Formula One may be used in combination (such as, of the parts by weight for X is 0

TABLE C active 100 X, Y X, Y X, Y ingredient 50 X, Y X, Y X, Y X, Y X, Y (Y) Parts 20 X, Y X, Y X, Y X, Y X, Y by weight 15 X, Y X, Y X, Y X, Y X, Y 10 X, Y X, Y 5 X, Y X, Y X, Y X, Y 3 X, Y X, Y X, Y X, Y X, Y X, Y X, Y 2 X, Y X, Y X, Y X, Y X, Y 1 X, Y X, Y X, Y X, Y X, Y X, Y X, Y X, Y X, Y 1 2 3 5 10 15 2O 50 100 molecule of Formula One (X) Parts by weight

0838 Ranges of weight ratios of a molecule of Formula Ibenzenesulfonates, alkyl sulfates, and non-ionic Surfactants One to an active ingredient may be depicted as X:Y to X: Such as ethylene oxide adducts of alkyl phenols. Y, wherein X and Y are defined as above. 0845 Emulsifiable concentrates of pesticides comprise a 0839. In one embodiment, the range of weight ratios may convenient concentration of a pesticide. Such as from about be X:Y to X: Y, wherein X >Y and X-Y. By way of 50 to about 500 grams per liter of liquid dissolved in a carrier non-limiting example, the range of a weight ratio of a that is either a water miscible solvent or a mixture of molecule of Formula One to an active ingredient may be water-immiscible organic solvent and emulsifiers. Useful between 3:1 and 1:3, inclusive of the endpoints. organic solvents include aromatics, especially Xylenes and 0840. In another embodiment, the range of weight ratios petroleum fractions, especially the high-boiling naphtha may be X:Y to X: Y, wherein X >Y and X->Y. By lenic and olefinic portions of petroleum Such as heavy way of non-limiting example, the range of weight ratio of a aromatic naphtha. Other organic solvents may also be used, molecule of Formula One to an active ingredient may be Such as the terpenic solvents including rosin derivatives, between 15:1 and 3:1, inclusive of the endpoints. aliphatic ketones such as cyclohexanone, and complex alco 0841. In another embodiment, the range of weight ratios hols such as 2-ethoxyethanol. Suitable emulsifiers for emul may be X:Y to X: Y, wherein X-Y and X-Y. By sifiable concentrates are selected from conventional anionic way of non-limiting example, the range of weight ratios of and non-ionic Surfactants. a molecule of Formula One to an active ingredient may be 0846 Aqueous Suspensions comprise Suspensions of between about 1:3 and about 1:20, inclusive of the end water-insoluble pesticides dispersed in an aqueous carrier at points. a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the Formulations pesticide and vigorously mixing it into a carrier comprised of water and Surfactants. Ingredients, such as inorganic salts 0842) A pesticide is rarely suitable for application in its and synthetic or natural gums may also be added, to increase pure form. It is usually necessary to add other Substances so the density and Viscosity of the aqueous carrier. It is often that the pesticide may be used at the required concentration most effective to grind and mix the pesticide at the same and in an appropriate form, permitting ease of application, time by preparing the aqueous mixture and homogenizing it handling, transportation, storage, and maximum pesticide in an implement such as a sand mill, ball mill, or piston-type activity. Thus, pesticides are formulated into, for example, homogenizer. baits, concentrated emulsions, dusts, emulsifiable concen 0847 Pesticides may also be applied as granular compo trates, fumigants, gels, granules, microencapsulations, seed sitions that are particularly useful for applications to the soil. treatments, Suspension concentrates, Suspoemulsions, tab Granular compositions usually contain from about 0.5% to lets, water Soluble liquids, water dispersible granules or dry about 10% by weight of the pesticide, dispersed in a carrier flowables, wettable powders, and ultra-low volume solu that comprises clay or a similar Substance. Such composi tions. tions are usually prepared by dissolving the pesticide in a 0843 Pesticides are applied most often as aqueous sus Suitable solvent and applying it to a granular carrier which pensions or emulsions prepared from concentrated formu has been pre-formed to the appropriate particle size, in the lations of Such pesticides. range of from about 0.5 to about 3 mm. Such compositions 0844. Such water-soluble, water-suspendable, or emulsi may also be formulated by making a dough or paste of the fiable formulations are either solids, usually known as carrier and molecule and crushing and drying to obtain the wettable powders, or water dispersible granules, or liquids desired granular particle size. usually known as emulsifiable concentrates, or aqueous 0848 Dusts containing a pesticide are prepared by inti Suspensions. Wettable powders, which may be compacted to mately mixing the pesticide in powdered form with a form water dispersible granules, comprise an intimate mix Suitable dusty agricultural carrier, such as kaolin clay, ture of the pesticide, a carrier, and Surfactants. The concen ground Volcanic rock, and the like. Dusts can Suitably tration of the pesticide is usually from about 10% to about contain from about 1% to about 10% of the pesticide. Dusts 90% by weight. The carrier is usually selected from among may be applied as a seed dressing or as a foliage application the attapulgite clays, the montmorillonite clays, the diato with a dust blower machine. maceous earths, or the purified silicates. Effective surfac 0849. It is equally practical to apply a pesticide in the tants, comprising from about 0.5% to about 10% of the form of a solution in an appropriate organic solvent, usually wettable powder, are found among Sulfonated lignins, con petroleum oil. Such as the spray oils, which are widely used densed naphthalenesulfonates, naphthalenesulfonates, alky in agricultural chemistry. US 2017/020880.6 A1 Jul. 27, 2017 79

0850 Pesticides can also be applied in the form of an used for two main functions in agrochemical formulations: aerosol composition. In such compositions the pesticide is during processing and manufacture to increase the rate of dissolved or dispersed in a carrier, which is a pressure wetting of powders in water to make concentrates for generating propellant mixture. The aerosol composition is soluble liquids or Suspension concentrates; and during mix packaged in a container from which the mixture is dispensed ing of a product with water in a spray tank to reduce the through an atomizing valve. wetting time of wettable powders and to improve the pen 0851 Pesticide baits are formed when the pesticide is etration of water into water-dispersible granules. Examples mixed with food or an attractant or both. When the pests eat of wetting agents used in wettable powder, Suspension the bait they also consume the pesticide. Baits may take the concentrate, and water-dispersible granule formulations are: form of granules, gels, flowable powders, liquids, or Solids. Sodium lauryl Sulfate; sodium dioctyl sulfo Succinate; alkyl Baits may be used in pest harborages. phenol ethoxylates; and aliphatic alcohol ethoxylates. 0852. Fumigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in Sufficient 0858. A dispersing agent is a substance which adsorbs concentrations to kill pests in Soil or enclosed spaces. The onto the surface of particles and helps to preserve the state toxicity of the fumigant is proportional to its concentration of dispersion of the particles and prevents them from and the exposure time. They are characterized by a good reaggregating. Dispersing agents are added to agrochemical capacity for diffusion and act by penetrating the pests formulations to facilitate dispersion and Suspension during respiratory system or being absorbed through the pests manufacture, and to ensure the particles redisperse into cuticle. Fumigants are applied to control stored product water in a spray tank. They are widely used in wettable pests under gas proof sheets, in gas sealed rooms or build powders, Suspension concentrates and water-dispersible ings or in special chambers. granules. Surfactants that are used as dispersing agents have 0853 Pesticides may be microencapsulated by suspend the ability to adsorb strongly onto a particle Surface and ing the pesticide particles or droplets in plastic polymers of provide a charged or steric barrier to reaggregation of various types. By altering the chemistry of the polymer or by particles. The most commonly used surfactants are anionic, changing factors in the processing, microcapsules may be non-ionic, or mixtures of the two types. For wettable powder formed of various sizes, solubility, wall thicknesses, and formulations, the most common dispersing agents are degrees of penetrability. These factors govern the speed with Sodium lignoSulfonates. For Suspension concentrates, very which the active ingredient within is released, which in turn, good adsorption and stabilization are obtained using poly affects the residual performance, speed of action, and odor electrolytes, such as Sodium naphthalene Sulfonate formal of the product. dehyde condensates. Tristyrylphenol ethoxylate phosphate 0854. Oil solution concentrates are made by dissolving esters are also used. Non-ionics such as alkylarylethylene pesticide in a solvent that will hold the pesticide in solution. oxide condensates and EO-PO block copolymers are some Oil solutions of a pesticide usually provide faster knock times combined with anionics as dispersing agents for down and kill of pests than other formulations due to the Suspension concentrates. In recent years, new types of very Solvents themselves having pesticidal action and the disso high molecular weight polymeric Surfactants have been lution of the waxy covering of the integument increasing the developed as dispersing agents. These have very long hydro speed of uptake of the pesticide. Other advantages of oil phobic backbones and a large number of ethylene oxide solutions include better storage stability, better penetration chains forming the teeth of a comb surfactant. These high of crevices, and better adhesion to greasy Surfaces. molecular weight polymers can give very good long-term 0855. Another embodiment is an oil-in-water emulsion, stability to suspension concentrates because the hydropho wherein the emulsion comprises oily globules which are bic backbones have many anchoring points onto the particle each provided with a lamellar liquid crystal coating and are Surfaces. Examples of dispersing agents used in agrochemi dispersed in an aqueous phase, wherein each oily globule cal formulations are: sodium lignoSulfonates; sodium naph comprises at least one molecule which is agriculturally thalene sulfonate formaldehyde condensates; tristyrylphenol active, and is individually coated with a monolamellar or ethoxylate phosphate esters; aliphatic alcohol ethoxylates; oligolamellar layer comprising: (1) at least one non-ionic alkyl ethoxylates: EO-PO block copolymers; and graft copo lipophilic Surface-active agent, (2) at least one non-ionic lymers. hydrophilic Surface-active agent and (3) at least one ionic 0859. An emulsifying agent is a substance which stabi Surface-active agent, wherein the globules having a mean lizes a Suspension of droplets of one liquid phase in another particle diameter of less than 800 nanometers. liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most Other Formulation Components commonly used emulsifier blends contain alkylphenol or 0856 Generally, when the molecules disclosed in For aliphatic alcohol with twelve or more ethylene oxide units mula One are used in a formulation, Such formulation can and the oil-soluble calcium salt of dodecylbenzenesulfonic also contain other components. These components include, acid. A range of hydrophile-lipophile balance (“HLB) val but are not limited to, (this is a non-exhaustive and non ues from 8 to 18 will normally provide good stable emul mutually exclusive list) wetters, spreaders, Stickers, pen sions. Emulsion stability can sometimes be improved by the etrants, buffers, sequestering agents, drift reduction agents, addition of a small amount of an EO-PO block copolymer compatibility agents, anti-foam agents, cleaning agents, and Surfactant. emulsifiers. A few components are described forthwith. 0860. A solubilizing agent is a surfactant which will form 0857. A wetting agent is a substance that when added to micelles in water at concentrations above the critical micelle a liquid increases the spreading or penetration power of the concentration. The micelles are then able to dissolve or liquid by reducing the interfacial tension between the liquid solubilize water-insoluble materials inside the hydrophobic and the Surface on which it is spreading. Wetting agents are part of the micelle. The types of surfactants usually used for US 2017/020880.6 A1 Jul. 27, 2017

solubilization are non-ionics, Sorbitan monooleates, Sorbitan production and in application through a spray tank. In order monooleate ethoxylates, and methyl oleate esters. to reduce the tendency to foam, anti-foam agents are often 0861 Surfactants are sometimes used, either alone or added either during the production stage or before filling with other additives such as mineral or vegetable oils as into bottles. Generally, there are two types of anti-foam adjuvants to spray-tank mixes to improve the biological agents, namely silicones and non-silicones. Silicones are performance of the pesticide on the target. The types of usually aqueous emulsions of dimethyl polysiloxane, while Surfactants used for bioenhancement depend generally on the non-silicone anti-foam agents are water-insoluble oils, the nature and mode of action of the pesticide. However, Such as octanol and nonanol, or silica. In both cases, the they are often non-ionics such as: alkyl ethoxylates; linear function of the anti-foam agent is to displace the Surfactant aliphatic alcohol ethoxylates; aliphatic amine ethoxylates. from the air-water interface. 0862. A carrier or diluent in an agricultural formulation is 0867 “Green’ agents (e.g., adjuvants, surfactants, sol a material added to the pesticide to give a product of the vents) can reduce the overall environmental footprint of crop required strength. Carriers are usually materials with high protection formulations. Green agents are biodegradable and absorptive capacities, while diluents are usually materials generally derived from natural and/or Sustainable sources, with low absorptive capacities. Carriers and diluents are e.g. plant and animal sources. Specific examples are: Veg used in the formulation of dusts, wettable powders, granules etable oils, seed oils, and esters thereof, also alkoxylated and water-dispersible granules. alkyl polyglucosides. 0863 Organic solvents are used mainly in the formula tion of emulsifiable concentrates, oil-in-water emulsions, Applications Suspoemulsions, and ultra-low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures 0868 Molecules of Formula One may be applied to any of solvents are used. The first main groups of solvents are locus. Particular crop loci to apply Such molecules include aliphatic paraflinic oils such as kerosene or refined paraffins. loci where alfalfa, almonds, , barley, beans, canola, The second main group (and the most common) comprises corn, cotton, crucifers, lettuce, oats, oranges, pears, peppers, the aromatic solvents such as Xylene and higher molecular potatoes, rice, Sorghum, soybeans, Strawberries, Sugarcane, weight fractions of C and Co aromatic solvents. Chlori Sugar beets, Sunflowers, tobacco, tomatoes, wheat, and other nated hydrocarbons are useful as cosolvents to prevent valuable crops are growing or the seeds thereof are going to crystallization of pesticides when the formulation is emul be planted. sified into water. Alcohols are sometimes used as cosolvents 0869 Molecules of Formula One may also be applied to increase solvent power. Other solvents may include where plants, such as crops, are growing and where there are vegetable oils, seed oils, and esters of vegetable and seed low levels (even no actual presence) of pests that can oils. commercially damage such plants. Applying Such molecules 0864. Thickeners or gelling agents are used mainly in the in Such locus is to benefit the plants being grown in Such formulation of Suspension concentrates, emulsions and Sus locus. Such benefits, may include, but are not limited to: poemulsions to modify the rheology or flow properties of the helping the plant grow a better root system; helping the plant liquid and to prevent separation and settling of the dispersed better withstand stressful growing conditions; improving the particles or droplets. Thickening, gelling, and anti-settling health of a plant; improving the yield of a plant (e.g. agents generally fall into two categories, namely water increased biomass and/or increased content of valuable insoluble particulates and water-soluble polymers. It is pos ingredients); improving the vigor of a plant (e.g. improved sible to produce Suspension concentrate formulations using plant growth and/or greener leaves); improving the quality clays and silicas. Examples of these types of materials, of a plant (e.g. improved content or composition of certain include, but are not limited to, montmorillonite, bentonite, ingredients); and improving the tolerance to abiotic and/or magnesium aluminum silicate, and attapulgite. Water biotic stress of the plant. soluble polysaccharides have been used as thickening-gell 0870. Molecules of Formula One may be applied with ing agents for many years. The types of polysaccharides ammonium Sulfate when growing various plants as this may most commonly used are natural extracts of seeds and provide additional benefits. seaweeds or are synthetic derivatives of cellulose. Examples 0871 Molecules of Formula One may be applied on, in, of these types of materials include, but are not limited to, or around plants genetically modified to express specialized guar gum, locust bean gum, carrageenam; alginates; methyl traits, such as Bacillus thuringiensis or other insecticidal cellulose; sodium carboxymethyl cellulose (SCMC); toxins, or those expressing herbicide resistance, or those hydroxyethyl cellulose (HEC). Other types of anti-settling with 'stacked' foreign genes expressing insecticidal toxins, agents are based on modified starches, polyacrylates, poly herbicide resistance, nutrition-enhancement, or any other vinyl alcohol and polyethylene oxide. Another good anti beneficial traits. Settling agent is Xanthan gum. 0872 Molecule of Formula One may be applied to the 0865 Microorganisms can cause spoilage of formulated foliar and/or fruiting portions of plants to control pests. Such products. Therefore preservation agents are used to elimi molecules will either come in direct contact with the pest, or nate or reduce their effect. Examples of such agents include, the pest will consume such molecules when eating the plant but are not limited to: propionic acid and its sodium salt; or while extracting sap from the plant. Sorbic acid and its sodium or potassium salts; benzoic acid 0873 Molecule of Formula One may also be applied to and its sodium salt; p-hydroxybenzoic acid sodium salt; the soil, and when applied in this manner, root and stem methyl p-hydroxybenzoate; and 1,2-benzisothiazolin-3-one feeding pests may be controlled. The roots may absorb Such (BIT). molecules thereby taking it up into the foliar portions of the 0866 The presence of surfactants often causes water plant to control above ground chewing and sap feeding based formulations to foam during mixing operations in pests. US 2017/020880.6 A1 Jul. 27, 2017

0874 Systemic movement of pesticides in plants may be administered orally to the animals with the drinking water or utilized to control pests on one portion of the plant by feed. The dosages and formulations that are Suitable depend applying (for example by spraying a locus) a molecule of on the species. Formula One to a different portion of the plant. For example, 0882 Molecules of Formula One may also be used for control of foliar-feeding insects may be achieved by drip controlling parasitic worms, especially of the intestine, in irrigation or furrow application, by treating the soil with for the animals listed above. example pre- or post-planting soil drench, or by treating the 0883 Molecules of Formula One may also be employed seeds of a plant before planting. in therapeutic methods for human health care. Such methods 0875 Molecules of Formula One may be used with baits. include, but are limited to, oral administration in the form of Generally, with baits, the baits are placed in the ground for example, tablets, capsules, drinks, granules, and by where, for example, termites can come into contact with, dermal application. and/or be attracted to, the bait. Baits can also be applied to 0884 Molecules of Formula One may also be applied to a surface of a building, (horizontal, Vertical, or slant Surface) invasive pests. Pests around the world have been migrating where, for example, ants, termites, cockroaches, and flies, to new environments (for Such pest) and thereafter becoming can come into contact with, and/or be attracted to, the bait. a new invasive species in Such new environment. Such 0876 Molecules of Formula One may be encapsulated molecules may also be used on Such new invasive species to inside, or placed on the Surface of a capsule. The size of the control them in Such new environments. capsules can range from nanometer size (about 100-900 0885 Consequently, in light of the above and the Tables nanometers in diameter) to micrometer size (about 10-900 in the Table Section, the following items are provided. microns in diameter). 1. A molecule having the following formula 0877 Molecules of Formula One may be applied to eggs of pests. Because of the unique ability of the eggs of some Formula One

pests to resist certain pesticides, repeated applications of Such molecules may be desirable to control newly emerged larvae. 0878 Molecules of Formula One may be applied as seed treatments. Seed treatment may be applied to all types of seeds, including those from which plants genetically modi fied to express specialized traits will germinate. Represen tative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, wherein: such as “Roundup Ready’ seed, or those with "stacked” 0886 (A) R', R. R. R'', R', and R' are each foreign genes expressing insecticidal toxins, herbicide resis independently selected from the group consisting of H, tance, nutrition-enhancement, drought resistance, or any F, Cl, Br, I, CN, (C-C)alkyl, (C-C)haloalkyl, (C- other beneficial traits. Furthermore, such seed treatments C.)alkoxy, and (C-C)haloalkoxy with molecules of Formula One may further enhance the 0887 preferably, R. R. R. R'', R', and R' are H; ability of a plant to better withstand stressful growing 0888 (B) R. R. and R are each independently conditions. This results in a healthier, more vigorous plant, selected from the group consisting of H. F. Cl, Br, I, which can lead to higher yields at harvest time. Generally, CN, (C-C)alkyl, (C-C)alkenyl, (C-C)alkynyl, about 1 gram of such molecules to about 500 grams per (C-C)haloalkyl, (C-C)alkoxy, and (C-C)ha 100,000 seeds is expected to provide good benefits, amounts loalkoxy from about 10 grams to about 100 grams per 100,000 seeds 0889 preferably, R, is C1, Br, or CH, R is F, Cl, Br is expected to provide better benefits, and amounts from or CH=CH, and R is C1, Br, or CH, about 25 grams to about 75 grams per 100,000 seeds is 0890 more preferably, R. R. and R is Cl; expected to provide even better benefits. 0891 (C) R' is (C-C)haloalkyl 0879 Molecules of Formula One may be applied with 0892 preferably R7 is CF, or CFCH: one or more active ingredients in a Soil amendment. (0893 (D) R is selected from the group consisting of 0880 Molecules of Formula One may be used for con (F), H, F, Cl, Br, I, CN, (C-C)alkyl, (C-C)haloalkyl, trolling endoparasites and ectoparasites in the veterinary (C-C)alkoxy, and (C-C)haloalkoxy medicine sector or in the field of non-human-animal keep 0894 preferably R is H: ing. Such molecules may be applied by oral administration 0895) (E) R' is selected from the group consisting of in the form of, for example, tablets, capsules, drinks, gran (F), F, Cl, Br, I, CN, (C-C)alkyl, (C-C)alkenyl, ules, by dermal application in the form of for example, (C-C)alkynyl, (C-C)haloalkyl, (C-C)alkoxy, and dipping, spraying, pouring on, spotting on, and dusting, and (C-C)haloalkoxy by parenteral administration in the form of for example, an 0896) preferably R' is C1, Br, CH, or CF; injection. (0897 (F) Rand R' together can optionally form a 3 0881 Molecules of Formula One may also be employed to 5-membered saturated or unsaturated, hydrocarbyl advantageously in livestock keeping, for example, cattle, link, sheep, pigs, chickens, salmon, and geese. They may also be 0898 wherein said hydrocarbyl link may optionally be employed advantageously in pets such as, horses, , and substituted with one or more substituents indepen cats. Particular pests to control would be fleas and ticks that dently selected from the group consisting of F, Cl, Br, are bothersome to such animals. Suitable formulations are I, and CN: US 2017/020880.6 A1 Jul. 27, 2017 82

0899 (G) Q is selected from the group consisting of O 11. A process to control a pest said process comprising or S applying to a locus, a pesticidally effective amount of a (0900 preferably Q is O: molecule according to any one of the 1, 2, 3, or 4. (0901 (H) L is (C-C)alkyl 12. A process to control a pest said process comprising (0902 preferably L is CHCH or CH(CH)CH: applying to a locus, a pesticidally effective amount of a (0903 (I) n is 0, 1, or 2: pesticidal composition according to any one of the 5, 6, 7, (0904 (J) R' is selected from the group consisting of 8, 9, or 10. (C-C)alkyl, (C-C)alkenyl, (C-C)cycloalkyl, (C- 13. A molecule according to any one of 1, 2, 3, or 4, or a C.)haloalkyl, (C-C)alkoxy, (C-C)haloalkoxy, and pesticidal composition according to any of 5, 6, 7, 8, 9, or phenyl, 10, wherein said molecule is in the form of agriculturally 0905 wherein each alkyl, alkenyl, cycloalkyl, acceptable acid addition salt. haloalkyl, alkoxy, haloalkoxy, and phenyl may option 14. A molecule according to any one of 1, 2, 3, or 4, or a ally be substituted with one or more substituents inde pesticidal composition according to any of 5, 6, 7, 8, 9, or pendently selected from the group consisting of F, Cl, 10, wherein said molecule is in the form of a salt derivative. Br, I, CN, and OH 15. A molecule according to any one of 1, 2, 3, or 4, or a (0906) preferably R'' is CHCH or CHCF; and pesticidal composition according to any of 5, 6, 7, 8, 9, or 0907 agriculturally acceptable acid addition salts, salt 10, wherein said molecule is in the form of solvate. derivatives, Solvates, ester derivatives, crystal poly 16. A molecule according to any one of 1, 2, 3, or 4, or a morphs, isotopes, resolved stereoisomers, and tautom pesticidal composition according to any of 5, 6, 7, 8, 9, or ers, of the molecules of Formula One. 10, wherein said molecule is in the form of an ester 2. A molecule according to 1 wherein derivative. (0908 (A) R', R, R, R, R2, and R are H: 17. A molecule according to any one of 1, 2, 3, or 4, or a (0909 (B) R. R. and R are each independently pesticidal composition according to any of 5, 6, 7, 8, 9, or selected from the group consisting of H, F, Cl, Br, 10, wherein said molecule is in the form of a crystal (C-C)alkyl, and (C-C)alkenyl: polymorph. (0910 (C) R' is (C-C)haloalkyl: 18. A molecule according to any one of 1, 2, 3, or 4, or a 0911 (D) R is H: pesticidal composition according to any of 5, 6, 7, 8, 9, or (0912 (E) R' is selected from the group consisting of 10, wherein said molecule has deuterium, tritium, and or Cl, Br, (C-C)alkyl, and (C-C)haloalkyl; 14C. 0913 (G) Q is O: 19. A molecule according to any one of 1, 2, 3, or 4, or a (0914 (H) L is (C-C)alkyl: pesticidal composition according to any of 5, 6, 7, 8, 9, or (0915 (I) n is 0, 1, or 2: 10, wherein said molecule is in the form of one or more (0916 (3) R' is selected from the group consisting of Stereoisomers (C-C)alkyl and (C-C)haloalkyl, 20. A molecule according to any one of 1, 2, 3, or 4, or a 0917 wherein each alkyl or haloalkyl may optionally pesticidal composition according to any of 5, 6, 7, 8, 9, or be substituted with one or more substituents indepen 10, wherein said molecule is in the form of a resolved dently selected from the group consisting of F, Cl, Br, Stereoisomer. I, CN, and OH. 21. A pesticidal composition according to any of 5, 6, 7, 8, 3. A molecule according to 1 wherein said molecule is 9, or 10, wherein said pesticidal composition further com selected from the group consisting of one of the molecules prises another active ingredient. in Table 2. 22. A pesticidal composition according to any of 5, 6, 7, 8, 4. A molecule according to 1 wherein said molecule is 9, or 10, wherein said pesticidal composition further com selected from the group consisting of one of the molecules prises two more active ingredients. in Table 1. 23. A pesticidal composition according to any of 5, 6, 7, 8, 5. A pesticidal composition comprising a molecule accord 9, or 10, wherein said active ingredient has a MOA different ing to any one of 1, 2, 3, or 4, further comprising one or more from the MoA of said molecule of Formula One. active ingredients. 24. A pesticidal composition according to any of 5, 6, 7, 8, 6. A pesticidal composition according to 5 wherein said 9, or 10, wherein said pesticidal composition comprises an active ingredient is from AIGA. active ingredient having acaricidal, algicidal, avicidal, bac 7. A pesticidal composition according to 5 wherein said tericidal, fungicidal, herbicidal, insecticidal, molluscicidal, active ingredient is selected from the group consisting of nematicidal, rodenticidal, and/or virucidal properties. AI-1, 1,3-dichloropropene, chlorpyrifos, chlorpyrifos 25. A pesticidal composition according to any of 5, 6, 7, 8, methyl, hexaflumuron, methoxyfenozide, noviflumuron, 9, or 10, wherein said pesticidal composition comprises an spinetoram, spinosad, Sulfoxaflor, and Sulfuryl fluoride. active ingredient that is an antifeedant, bird repellent, che 8. A pesticidal composition comprising a molecule accord mosterilant, herbicide Safener, insect attractant, insect repel ing to any one of 1, 2, 3, or 4, further comprising a MoA lent, mammal repellent, mating disrupter, plant activator, Material. plant growth regulator, and/or synergist. 9. A pesticidal composition according to 7 wherein said 26. A pesticidal composition according to any of 5, 6, 7, 8, MoA Material is from MOAMGA. 9, or 10, wherein said pesticidal composition comprises an 10. A pesticidal composition according to any one of 5, 6, 7, active ingredient that is a biopesticide. 8, or 9, wherein the weight ratio of the molecule according 27. A pesticidal composition according to any of 5, 6, 7, 8, to Formula One to said active ingredient is selected from 9, or 10, wherein said weight ratio of a molecule of Formula Table B. One to an active ingredient is 100:1 to 1:100. US 2017/020880.6 A1 Jul. 27, 2017

28. A pesticidal composition according to any of 5, 6, 7, 8, 42. A process according to 12 wherein said pest is from 9, or 10, wherein said weight ratio of a molecule of Formula Phylum Nematoda. One to an active ingredient is 50:1 to 1:50. 43. A process according to 12 wherein said pests are ants, 29. A pesticidal composition according to any of 5, 6, 7, 8, aphids, beetles, bristletails, cockroaches, crickets, earwigs, 9, or 10, wherein said weight ratio of a molecule of Formula fleas, flies, grasshoppers, leafhoppers, lice (including sea One to an active ingredient is 20:1 to 1:20 lice), locusts, mites, moths, nematodes, scales, Symphylans, 30. A pesticidal composition according to any of 5, 6, 7, 8, termites, thrips, ticks, wasps, and/or whiteflies. 9, or 10, wherein said weight ratio of a molecule of Formula 44. A process according to 12 wherein said locus is where One to an active ingredient is 10:1 to 1:10. alfalfa, almonds, apples, barley, beans, canola, corn, cotton, 31. A pesticidal composition according to any of 5, 6, 7, 8, crucifers, lettuce, oats, oranges, pears, peppers, potatoes, 9, or 10, wherein said weight ratio of a molecule of Formula rice, Sorghum, Soybeans, Strawberries, Sugarcane, Sugar One to an active ingredient is 5:1 to 1:5. beets, Sunflowers, tobacco, tomatoes, wheat, and other valu 32. A pesticidal composition according to any of 5, 6, 7, 8, able crops are growing or the seeds thereof are planted. 9, or 10, wherein said weight ratio of a molecule of Formula 45. A pesticidal composition according to any of 5, 6, 7, 8, One to an active ingredient is 3:1 to 1:3. 9, or 10, wherein said pesticidal composition further com 33. A pesticidal composition according to any of 5, 6, 7, 8, prises ammonium Sulfate. 9, or 10, wherein said weight ratio of a molecule of Formula 46. A process according to 12 wherein said locus is where One to an active ingredient is 2:1 to 1:2. plants genetically modified to express specialized traits are 34. A pesticidal composition according to any of 5, 6, 7, 8, planted. 9, or 10, wherein said weight ratio of a molecule of Formula One to an active ingredient is 1:1. 47. A process according to 12 wherein said applying is done 35. A pesticidal composition according to any of 5, 6, 7, 8, to the foliar and/or fruiting portions of plants. 9, or 10, wherein said weight ratio of a molecule of Formula 48. A process according to 12 wherein said applying is done One to an active ingredient is depicted as X:Y; wherein X is to the soil. the parts by weight of a molecule of Formula One and Y is 49. A process according to 12 wherein said applying is done the parts by weight of active ingredient; further wherein the by drip irrigation, furrow application, or pre- or post numerical range of the parts by weight for X is 0Y and X-Y. 52. A process comprising applying a molecule according to 37. A pesticidal composition according to 35 wherein a any one of 1, 2, 3, or 4, or a pesticidal composition according range of weight ratios of a molecule of Formula One to an to any of 5, 6, 7, 8, 9, or 10, to a seed. active ingredient is depicted as X:Y to X: Y; further 53. A process comprising applying a molecule according to wherein X >Y and X->Y. 1, 2, 3, or 4, to a locus that includes a non-human animal to 38. A pesticidal composition according to 35 wherein a control endoparasites and/or ectoparasites. range of weight ratios of a molecule of Formula One to an 54. A process to produce a pesticidal composition, said active ingredient is depicted as X:Y to X: Y; further process comprising mixing a molecule according to any one wherein X-Y and X-Y. of claims 1, 2, 3, or 4, with one or more active ingredients. 39. A pesticidal composition according to 35 wherein said 0918. The headings in this document are for convenience composition is synergistic. only and must not be used to interpret any portion hereof. 40. A process according to 12 wherein said pest is from Phylum Arthropoda. Table Section 41. A process according to 12 wherein said pest is from Phylum Mollusca. 0919 TABLE 2

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

13 US 2017/020880.6 A1 Jul. 27, 2017 84

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F2 15

F3 16

F4 13

F5 16

F6 15

F7 13 US 2017/020880.6 A1 Jul. 27, 2017 85

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F8 15

F9 16

F10 F 13

F11 F 15

F12 F 16 US 2017/020880.6 A1 Jul. 27, 2017 86

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F13 13

13

C 21 CH3

C

C

F15 F 13

F16 F 13

F17 F 14

F18 F 14 US 2017/020880.6 A1 Jul. 27, 2017 87

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F19 14

F2O F 14

F21 F 14

F22 F 15

F23 F 16 US 2017/020880.6 A1 Jul. 27, 2017 88

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F24 14

F25 F 15

F26 F 16

F27 F 16

F28 F 16

F29 F 14 US 2017/020880.6 A1 Jul. 27, 2017 89

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F30 14

F31 F 16

F32 F 14

F33 14

F34 F 16 US 2017/020880.6 A1 Jul. 27, 2017 90

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F35 14

F36 F 14

F37 F 16

F38 CH 13 F F F F F C H O F O 2 O NF W F C M {uk F C O CH, O

F39 CH3 13 F F F F F C 2 F H N F C S F C O CH F US 2017/020880.6 A1 Jul. 27, 2017 91

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F40 14

F41 F 14

F42 F 15

F43 F 14

F44 16

F45 F 15 US 2017/020880.6 A1 Jul. 27, 2017 92

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F46 15

F47 14

F48 14

F49 F 18

FSO F 18

F51 F 17 US 2017/020880.6 A1 Jul. 27, 2017 93

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F52 14

F53 14

F54 14

F55 14

F56 15

F57 13 US 2017/020880.6 A1 Jul. 27, 2017 94

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F58 13

F59 14

F60 14

F61 14

F62 14

F63 15 US 2017/020880.6 A1 Jul. 27, 2017 95

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F64 14

F65 15

F66 16

F67 15

F68 16

F69 14 US 2017/020880.6 A1 Jul. 27, 2017 96

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F70 34

F71 13

F72 F 35

enantiomerically pure

F73 13

F75 17 US 2017/020880.6 A1 Jul. 27, 2017 97

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F77 14

F78 F 14

F79 F 14

F8O F 13

F81 F 14 US 2017/020880.6 A1 Jul. 27, 2017 98

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F82 17

F83 17

F84 29

F85 18

F86 18

F87 18 US 2017/020880.6 A1 Jul. 27, 2017 99

TABLE 2-continued

Structure and Preparation Method for F Series Molecules

No. Structure Prep.*

F88 18

F89 29

F90 18

F91 F 13

| F 1k F F O CH O

F92 F 29