(12) United States Patent
`Tobler et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 9,314,022 B2
`Apr. 19, 2016
`
`US009314022B2
`
`(54) FUNGICIDAL COMPOSITIONS
`(71) Applicant: Syngenta Crop Protection, LLC,
`Greensboro, NC (US)
`(72) Inventors: Hans Tobler, Basel (CH); Harald
`Walter, Stein (CH); Ulrich Johannes
`Haas, Stein (CH)
`(73) Assignee: Syngenta Crop Protection, LLC,
`Greensboro, NC (US)
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`(21) Appl. No.: 14/031.538
`(22) Filed:
`Sep.19, 2013
`
`(*) Notice:
`
`(65)
`
`Prior Publication Data
`US 2014/OO24532 A1
`Jan. 23, 2014
`
`Related U.S. Application Data
`(62) Division of application No. 12/597,221, filed as
`application No. PCT/EP2008/003279 on Apr. 23,
`2008, now Pat. No. 8,551,912.
`Foreign Application Priority Data
`
`(30)
`
`Apr. 25, 2007 (EP) ..................................... O70O8370
`
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`(51) Int. Cl.
`AOIN 43/56
`AOIN 43/40
`AOIN 43/54
`AOIN 43/653
`AOIN 43/84
`AOIN 55/10
`AOIN 43/50
`AOIN 55/00
`AOIN 57/20
`(52) U.S. Cl.
`CPC ................ A0IN 43/56 (2013.01); A0IN 43/40
`(2013.01); A0IN 43/50 (2013.01); A0IN 43/54
`(2013.01); A0IN 43/653 (2013.01): A0IN
`43/84 (2013.01); A0IN 55/00 (2013.01); A0IN
`57/20 (2013.01)
`
`(58) Field of Classification Search
`USPC .................................................. 514/383, 406
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`5/1997 Barry et al.
`5,627,061 A
`5/1997 Barry et al.
`5,633,435 A
`7/1998 Barry et al.
`5,776,760 A
`9/1998 Barry et al.
`5,804,425 A
`2f1999 Eichholtz et al.
`5,866,775 A
`6/1999 Martinell et al.
`5,914.451 A
`2/2000 Li et al.
`6,020,332 A
`9/2002 Wachendorff-Neumann et al.
`6,444,693 B1
`2007/0244121 A1* 10, 2007 Walter ................... AON 43.56
`514,237.5
`2/2008 Ehrenfreund .......... AON 43/32
`514,406
`
`2008/0051446 A1
`
`FOREIGN PATENT DOCUMENTS
`
`CA
`CN
`CN
`CN
`CN
`EP
`EP
`EP
`EP
`KR
`
`2, 2003
`2454298 A
`8, 1996
`1167.568. A
`8, 1997
`1155977 A
`1705668 A 12/2005
`101.035432 A
`9, 2007
`O353191, A2
`7, 1989
`O3922.25 A2
`3, 1990
`O86O438 A1
`2, 1997
`O936.213 A1
`8, 1999
`10-2005-0055767 A
`6, 2005
`(Continued)
`OTHER PUBLICATIONS
`
`HCAPLUS Abstract 1987: 151486 (1987).*
`HCAPLUS Abstract 1987:419367 (1987).*
`Issac, S., “What is the mode of action of fungicides and how do
`fungicides develop resistance?' Mycologist, vol. 13, Part 1, pp. 38-39
`(1999).*
`CABA abstract 1997:75026 (1997).
`CABA abstract 2005:80841 (2005).
`(Continued)
`
`Primary Examiner — John Pak
`(74) Attorney, Agent, or Firm — R. Kody Jones
`
`ABSTRACT
`(57)
`A composition Suitable for control of diseases caused by
`phytopathogens comprising (A) a compound of formula I
`
`(I)
`
`X
`
`X,
`
`O
`
`N NH
`
`N-N
`V
`CH
`
`4,723,984. A * 2/1988 Holmwood et al. .......... 504/272
`4,906,652 A * 3/1990 Karbach et al. ............... 514,383
`4,940,835 A
`7, 1990 Shah et al.
`4,971,908 A 11, 1990 Kishore et al.
`5,145,783 A
`9, 1992 Kishore et al.
`5,188,642 A
`2f1993 Shah et al.
`5,310,667 A
`5, 1994 Eichholtz et al.
`5,312.910 A
`5, 1994 Kishore et al.
`5,463,175
`10/1995 Barry et al.
`A
`
`wherein R is difluoromethyl or trifluoromethyl and X is
`chloro, fluoro or bromo; and (B) at least one compound
`selected from compounds known for their fungicidal activity;
`and a method of controlling diseases on useful plants, espe
`cially rust diseases on Soybean plants.
`
`17 Claims, No Drawings
`
`SYNGENTA EXHIBIT 1006
`Syngenta v. UPL, PGR2023-00017
`
`

`

`US 9,314,022 B2
`Page 2
`
`(56)
`
`References Cited
`
`FOREIGN PATENT DOCUMENTS
`
`RU
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`WO
`
`10, 2004
`2237996
`9533818 A2 12/1995
`9619442 A1
`6, 1996
`984.6607 A1
`10, 1998
`99.14187 A1
`3, 1999
`9942447 A1
`8, 1999
`O187822 A1
`11 2001
`O194339 A1
`12/2001
`O3070705 A1
`8, 2003
`O3074491 A1
`9, 2003
`2004O16088 A2
`2, 2004
`2004035589
`4/2004
`2004067528 A1
`8, 2004
`2005085234 A2
`9, 2005
`2006037632
`4/2006
`2006.108552
`10, 2006
`2006120219 A1
`11 2006
`2007OO9661
`1, 2007
`2007O 17450 A1
`2, 2007
`2007048556
`5/2007
`20070934O2 A1
`8, 2007
`OTHER PUBLICATIONS
`Godoy, C.V. et al., “Protective curative and eradicative effects of
`fungicides to control Soybean rust cuasued by Phakopsora
`pachyrhizi, in greenhouse. Fitopatologia Brasileira, vol. 29(1), pp.
`97-101 (2004).
`International Search Report and Written Opinion dated Dec. 9, 2008
`for International Patent Application No. PCT/EP2008/003279.
`Pilling, E.D. et al: "Azoxystrobin: Fate and Effects in the Terrestrial
`Environment” in: Brighton Crop Protection Conference, pp. 816-22.
`(1996).
`
`Godoy, Claudia V. etal: "Efeitos Protetor, Curativo e Erradicante de
`Fungicidas no Controle da Ferrugem da Soja Causada por
`Phakopsora pachyrhizi, em Casa de Vegetacao” in: Fitopatol 29/1
`(2004), pp. 97-101.
`Hayashi, Sei-ichi et al: “Convenient Procedures for Conversion of
`Carbonyl Compounds to
`-Difluoroolefins and their Selective
`Reductions to Monofluoroolefins' in: Chemistry Letters (1979), pp.
`983-86.
`of an
`Reactivity
`and
`"Preparation
`Minoru:
`Suda,
`a-(Difluororomethylene)-y-Lactone” in: Tetrahedron Letters 22/15
`(1981), pp. 1421-24.
`Wang, Jianji et al.: “Aminolysis of Esters or Lactones Promoted by
`NaHMDS-A General and Efficient Method for the Preparation of
`N-Aryl Amides' in: Synlett 9 (2001). Thieme Stuttgart & New York,
`pp. 1485-87.
`Cabre, Juan et al.: “New Experimental Strategies in Amide Synthesis
`using N,N-Bis2-oxo-3-oxazolidinylphosphorodiamidic Chloride'
`in: Synthesis (1984), pp. 413-17.
`Hans-Dieter, Martin et al.: “PE- and 13C-NMR-spektroskopische
`Untersuchungen
`Zur
`Homokonjugation
`in
`7-Alkyliden
`norbornadienen' in: Chemische Berichte 118 (1985), pp. 2514-43.
`CAS Registry Number: 72178-02-0.
`CAS 3251.56-49-8.
`CAS 348635-87-0.
`CAS 581809-46-3.
`CAS 658066-35-4.
`CaS 72178-02-0.
`Colby, S.R.: "Calculating synergistic and antagonistic responses of
`herbicide combination” in: Weeds vol. 15 (1967), pp. 20-22.
`Issac, S., What is the mode of action of fungicides and how do
`fungicides develop resistance?. Mycologist, 1999, 13(Part1):38-39.
`
`* cited by examiner
`
`

`

`1.
`FUNGCDAL COMPOSITIONS
`
`US 9,314,022 B2
`
`This application is a divisional of U.S. patent application
`Ser. No. 12/597,221 filed Mar. 10, 2010, which was a 371 of
`International Application No. PCT/EP2008/003279 filed
`Apr. 23, 2008, which claims priority to EP 07008370.4 filed
`Apr. 25, 2007, the contents of which are all incorporated
`herein by reference.
`The present invention relates to novel fungicidal composi
`tions Suitable for control of diseases caused by phytopatho
`gens, especially phytopathogenic fungi and to a method of
`controlling diseases on useful plants, especially rust diseases
`on Soybean plants.
`It is known from WO 04/35589 and WO 06/37632 that
`certain tricyclic amine derivatives and mixtures comprising
`said amine derivatives have biological activity against phyto
`pathogenic fungi. On the other hand various fungicidal com
`pounds of different chemical classes are widely known as
`plant fungicides for application in various crops of cultivated
`plants. However, crop tolerance and activity against phyto
`pathogenic plant fungi do not always satisfy the needs of
`agricultural practice in many incidents and aspects. For
`example, in the past in the most important regions for soybean
`cultures no economically significant phytopathogens were
`known. However, recently there has been an increase in
`severe rust infections of soybean crops in South America by
`the harmful fungus Phakopsora pachyrhizi resulting in con
`siderable yield losses. Most customary fungicides are unsuit
`able for controlling rust in soybeans or their action against
`Phakopsora pachyrhizi is unsatisfactory.
`Out of the above-mentioned needs of agricultural practice
`for increased crop tolerance and/or increased activity against
`phytopathogenic fungi, Such as Phakopsora pachyrhizi, there
`is therefore proposed in accordance with the present inven
`tion a novel composition Suitable for control of diseases
`caused by phytopathogens comprising
`a composition Suitable for control of diseases caused by
`phytopathogens comprising
`(A) a compound of formula I
`
`5
`
`10
`
`15
`
`25
`
`30
`
`35
`
`40
`
`(I)
`
`45
`
`2
`anilazine, arsenates, benalaxyl, benalaxyl-M, benodanil,
`benomyl, benthiavalicarb, benthiavalicarb-isopropyl, biphe
`nyl, bitertanol, blasticidin-S, bordeaux mixture, boscalid,
`bupirimate, cadmium chloride, captafol, captan, carbenda
`Zim, carbon disulfide, carboxin, carpropamid, cedar leaf oil,
`chinomethionat, chlorine, chloroneb, chlorothalonil, chloZo
`linate, cinnamaldehyde, copper, copper ammoniumcarbon
`ate, copper hydroxide, copper octanoate, copper oleate, cop
`per Sulphate, cyaZofamid, cycloheximide, cymoxaniil,
`dichlofluanid, dichlone, dichloropropene, diclocymet,
`diclomezine, dicloran, diethofencarb, diflumetorim, dime
`thirimol, dimethomorph, dinocap, dithianon, dodine, edifen
`phos, ethaboxam, ethirimol, etridiazole, famoxadone, fena
`midone, fenaminosulf, fenamiphos, fenarimol, fenfuram,
`fenhexamid, fenoxanil, fenpiclonil, fentin acetate, fentin
`chloride, fentin hydroxide, ferbam, ferimzone, fluazinam,
`fludioxonil, flusulfamide, flusulfamide, flutolanil, folpet,
`formaldehyde, fosetyl-aluminium, fthalide, fuberidazole,
`furalaxyl, furametpyr, flyodin, fuazatline, hexachloroben
`Zene, hymexazole, iminoctadine, iodocarb, iprobenfos,
`iprodione, iprovalicarb, isoprothiolane, kasugamycin, man
`coZeb, maneb, manganous dimethyldithiocarbamate,
`mefenoxam, mepronil, mercuric chloride, mercury, metal
`axyl, methasulfocarb, metiram, metrafenone, nabam, neem
`oil (hydrophobic extract), nuarimol, octhillinone, ofurace,
`oxadixyl, oxine copper, oXolinic acid, oxycarboxin, oxytet
`racycline, paclobutrazole, paraffin oil, paraformaldehyde,
`pencycuron, pentachloronitrobenzene, pentachlorophenol,
`penthiopyrad, perfurazoate, phosphoric acid, polyoxin, poly
`oxin D Zinc salt, potassium bicarbonate, probenazole, pro
`cymidone, propamocarb, propineb, produinazid, prothiocarb,
`pyrazophos, pyrifenox, pyroquilon, quinoxyfen, quintoZene,
`silthiofam, Sodium bicarbonate, sodium diacetate, sodium
`propionate, streptomycin, sulphur, TCMTB, tecloftalam, tec
`naZene, thiabendazole, thifluZamide, thiophanate, thiophan
`ate-methyl, thiram, tolclofoS-methyl, tolyfluanid, triaZOxide,
`trichoderma harzianum, tricyclazole, triforine, triphenyltin
`hydroxide, validamycin, VincloZolin, Zineb, Ziram, Zoxam
`ide, 1,1-bis(4-chlorophenyl)-2-ethoxyethanol. 2,4-dichlo
`rophenyl benzenesulfonate, 2-fluoro-N-methyl-N-1-naph
`thylacetamide, 4-chlorophenyl phenyl sulfone,
`
`50
`
`a compound of formula B-5.1
`
`N
`
`(B-5.1)
`
`R
`
`\
`
`N-N
`
`55
`
`60
`
`C
`
`65
`
`O
`
`o1N
`
`CH3
`
`wherein R is difluoromethyl or trifluoromethyl and X is
`chloro, fluoro or bromo; and
`(B) at least one compound selected from the group consist
`ing of
`(B1) a strobilurin fungicide,
`(B2) an azole fungicide,
`(B3) a morpholine fungicide,
`(B4) an anilinopyrimidine fungicide,
`(B5) a fungicide selected from the group consisting of
`
`

`

`3
`a compoundof formula B-5.2
`
`4
`a compoundof formula B-5.6
`
`US 9,314,022 B2
`
`(B-5.6)
`
`CH3,
`
`oO
`
`0.
`
`NH
`
`Cl
`
`(B-5.7)
`
`H3C
`,
`
`N.
`S
`
`ZA
`
`N.
`o” S
`
`CH;
`
`20
`
`a compoundof formula B-5.7
`
`[0
`\ANN
`fs“X CH;,
`N
`|
`o
`aON,
`
`/ So
`
`N p
`
`CH;
`
`p
`Br
`
`F
`
`3-difluoromethyl]-1-methyl-1H-pyrazole-4-carboxylic
`acid
` (2-bicyclopropyl-2-yl-phenyl)-amide
`(compound
`B-5.8), 3-difluoromethy]-1-methyl-1 H-pyrazole-4-carboxy-
`lic acid (9-isopropyp-1,2,3,4-tetrahydro-1,4-methano-naph-
`thalen-5-yl)-amide
`(compound B-5.9),
`1,3-dimethyl-5-
`fluoro-1 H-pyrazole-4-carboxylic
`acid
`[2-(1,3-
`dimethylbutyl)phenyl]-amide
`(compound
`B-5.10),
`3-difluoromethy]-1-methyl-1H-pyrazole-4-carboxylic
`acid
`(3',4'-dichloro-5-fluoro-1 ,1'-biphenyl-2-yl)-amide
`(com-
`pound B-5.11), N-{2-[3-chloro-5-(trifluoromethy])pyridin-
`2-yllethyl}-2-(trifluoromethyl)benzamid
`(compound
`B-5.12),
`3-difluoromethy]-1-methyl-1H-pyrazole-4-car-
`boxylic acid N-[2-(1,1,2,2-tetrafluoroethoxy)phenyl]-amide
`(compound B-5.13), 3-difluoromethyl-1-methyl-1H-pyra-
`zole-4-carboxylic
`acid N-[2-(1,1,2,3,3,3-hexafluoropro-
`poxy)phenyl]-amide (compound B-5.14), 3-difluoromethyl-
`1-methyl-1H-pyrazole-4-carboxylic acid N-[2-(2-chloro-1,
`1,2-trifluoroethoxy)phenyl]-amide
`(compound B-5.15),
`3-difluoromethy]-1-methyl-1H-pyrazole-4-carboxylic
`acid
`N-(4'-trifluoromethyl-biphen-2-yl)-amide
`(compound
`B-5.16),
`3-difluoromethy]-1-methyl-1H-pyrazole-4-car-
`boxylic
`acid N-(2'-triftuoromethyl-biphen-2-yl)-amide
`(compound B-5.17) and 3-difluoromethyl-1-methyl-1H-
`pyrazole-4-carboxylic acid N-(2'-trifluoromethyl-biphen-2-
`yl)-amide (compound B-5.18);
`(B6) a plant-bioregulator
`selected from the group consisting of
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`(B-5.2)
`
`(B-5.3)
`
`(B-5.4)
`
`(B-5.5)
`
`CH;
`
`F
`
`N
`
`Nw
`
`N
`
`NN
`
`¢ aA A
`
`N
`
`N
`
`F;
`
`®
`
`cl
`
`a compoundof formula B-5.3
`
`XY-
`
`SSN
`
`HN
`
`Cl
`
`oO
`
`a compoundof formula B-5.4
`
`CF,
`
`N*~
`
`O
`
`O
`
`N
`
`F
`
`F
`
`>
`
`a compoundof formula B-5.5
`
`OCHF,
`
`N
`
`O
`
`

`

`US 9,314,022 B2
`
`5
`acibenzolar-S-methyl, chlormeduat chloride, ethephon,
`mepiduat chloride and trinexapc-ethyl,
`(B7) an insecticide selected from the group consisting of
`abamectin, clothianidin, emamectin benzoate, imidaclo- 5
`prid, tefluthrin, thiamethoxam,
`and a compound of formula IV
`
`6
`-continued
`
`R
`3
`
`R
`
`(IV) 10
`
`2 N
`
`R3
`
`s
`
`(X.6)
`
`(X7)
`
`(Xs)
`
`15
`
`2O
`
`2 and
`
`R3
`
`N N
`\ i?
`
`N
`
`C
`
`O
`
`CS
`
`N
`
`le
`
`s
`
`X
`
`NH
`
`O
`
`HN
`n R
`
`wherein X is a bivalent group selected from
`
`25
`
`R4
`
`N-NH
`
`R3
`
`N
`2
`N
`
`R4
`
`R4
`
`R4
`
`N
`R4 /
`(
`N
`K
`
`S
`
`s
`
`R3
`
`R3
`
`R3
`
`R3
`
`s
`
`s
`
`s
`
`(X) 30
`
`wherein
`a) R is cyclopropyl Substituted by cyclopropyl at the 1-po
`sition, R is bromine, R is methyl, R is CN and X is X:
`b) R is methyl substituted by cyclopropyl, R is CF, R is
`35 methyl, R is C1 and X is X:
`c) R is cyclopropyl Substituted by cyclopropyl at the 1-po
`sition, R is CF, R is methyl, R is C1 and X is X;
`d) R is cyclopropyl Substituted by cyclopropyl at the 1-po
`40 sition, R is CF, R is methyl, R is CN and X is X:
`e) R is cyclopropyl Substituted by cyclopropyl at the 1-po
`sition, R is OCHCF. R is methyl, R is ON and X is X:
`f) R is isopropyl, R is methoxy; R is methyl, R is hydro
`as gen and X is Xs:
`g) R is isopropyl, R is trifluoromethyl, R is chlorine, R.
`is hydrogen and X is Xs:
`h) R is isopropyl, R is trifluoromethyl, R is methyl, R is
`hydrogen and X is Xs:
`i)R is methyl, R is bromine, R is methyl, R is CN and X
`is X;
`j) R is methyl, R is bromine, R is methyl, R is Cland X
`is X; and (B8) glyphosate, a compound of formula V
`
`50
`
`55
`
`(X2)
`
`(X3)
`
`(X4)
`
`OH
`
`O
`
`CH
`O
`N-1--" "
`
`(V)
`
`a NN
`
`(Xs)
`
`60
`
`65
`
`

`

`7
`fomesafen, and (B9) a racemic compound of formula VIa
`(syn)
`
`US 9,314,022 B2
`
`H
`
`CH3
`CH3,
`
`H
`
`O
`
`Ra7
`
`N
`n
`
`CH3
`
`N
`
`V "
`
`(VIa)
`
`5
`
`10
`
`15
`
`O
`
`N NH
`
`N-N
`V
`CH
`
`8
`
`X,
`
`(I)
`
`wherein Ra, is trifluoromethyl or difluoromethyl; a racemic
`mixture of formula VIb (anti)
`
`H
`
`H
`CH3,
`
`CH3
`
`O
`
`N
`V
`
`Ra7
`
`N
`
`CH
`
`25
`
`(VIb)
`
`30
`
`35
`
`40
`
`wherein Ra, is trifluoromethyl or difluoromethyl; a com
`pound of formula VIc
`
`(VIc)
`
`45
`
`50
`
`55
`
`H
`CH3,
`
`CH3
`
`O
`
`Ra7
`
`)
`
`N
`
`CH
`
`N
`V
`
`"
`
`which is an epimeric mixture of racemic compounds of
`formulae F-10 (syn) and F-11 (anti), wherein the ratio from
`racemic compounds of formula F-10 (syn) to racemic com
`pounds of formula F-11 (anti) is from 1000:1 to 1:1000 and
`wherein Ra, is trifluoromethyl or difluoromethyl.
`Preferred compositions comprising (A) a compound of
`formula I
`
`60
`
`65
`
`wherein R is difluoromethyl or trifluoromethyl and X is
`chloro, fluoro or bromo; and
`(B) a compound selected from the group consisting of
`(B1) a strobilurin fungicide. (B2) an azole fungicide. (B3)
`a morpholine fungicide, (B4) an anilinopyrimidine fungicide,
`(B5) a fungicide selected from the group consisting of anila
`zine (878), arsenates, benalaxyl (56), benalaxyl-M, benodanil
`(896), benomyl (62), benthiavalicarb, benthiavalicarb-iso
`propyl (68), biphenyl (81), bitertanol (84), blasticidin-S (85),
`bordeaux mixture (87), boscalid (88), bupirimate (98), cad
`mium chloride, captafol (113), captain (114), carbendazim
`(116), carbon disulfide (945), carboxin (120), carpropamid
`(122), cedar leaf oil, chinomethionat (126), chlorine, chlor
`oneb (139), chlorothalonil (142), chlozolinate (149), cinna
`maldehyde, copper, copper ammoniumcarbonate, copper
`hydroxide (169), copper octanoate (170), copper oleate, cop
`per sulphate (87), cyazofamid (185), cycloheximide (1022),
`cymoxanil (200), dichlofluanid (230), dichlone (1052),
`dichloropropene (233), diclocymet (237), diclomezine (239).
`dicloran (240), diethofencarb (245), diflumetorim (253),
`dimethirimol (1082), dimethomorph (263), dinocap (270),
`dithianon (279), dodine (289), edifenphos (290), ethaboxam
`(304), ethirimol (1133), etridiazole (321), famoxadone (322),
`fenamidone (325), fenaminosulf (1144), fenamiphos (326),
`fenarimol (327), fenfuram (333), fenhexamid (334), fenoxa
`nil (338), fenpiclonil (341), fentin acetate (347), fentin chlo
`ride, fentin hydroxide (347), ferbam (350), ferimZone (351),
`fluazinam (363), fludioxonil (368), flusulfamide (394), fluto
`lanil (396), folpet (400), formaldehyde (404), fosetyl-alu
`minium (407), fthalide (643), fuberidazole (419), furalaxyl
`(410), furametpyr (411), flyodin (1205), fuazatine (422),
`hexachlorobenzene (434), hymexazole, iminoctadine (459),
`iodocarb (3-Iodo-2-propynyl butyl carbamate), iprobenfos
`(IBP) (469), iprodione (470), iprovalicarb (471), isoprothi
`olane (474), kasugamycin (483), mancoZeb (496), maneb
`(497), manganous dimethyldithiocarbamate, mefenoxam
`(Metalaxyl-M) (517), mepronil (510), mercuric chloride
`(511), mercury, metalaxyl (516), methasulfocarb (528), meti
`ram (546), metrafenone, nabam (566), neem oil (hydrophobic
`extract), nuarimol (587), octhillinone (590), ofurace (592),
`oxadixyl (601), oxine copper (605), oxolinic acid (606), oxy
`carboxin (608), oxytetracycline (611), paclobutrazole (612),
`paraffin oil (628), paraformaldehyde, pencycuron (620), pen
`tachloronitrobenzene (716), pentachlorophenol (623),
`penthiopyrad, perfurazoate, phosphoric acid, polyoxin (654),
`polyoxin D Zinc salt (654), potassium bicarbonate, probena
`Zole (658), procymidone (660), propamocarb (668), propineb
`(676), produinazid (682), prothiocarb (1361), pyrazophos
`(693), pyrifenox (703), pyroquilon (710), quinoxyfen (715),
`quintozene (PCNB) (716), silthiofam (729), sodium bicar
`bonate, sodium diacetate, Sodium propionate, Streptomycin
`
`

`

`9
`(744), sulphur (754), TCMTB, tecloftalam, tecnazene
`(TCNB) (767), thiabendazole (790), thifluzamide (796),
`thiophanate (1435), thiophanate-methyl (802), thiram (804),
`tolclofos-methyl (808), tolylfluanid (810), triazoxide (821),
`trichoderma harzianum (825), tricyclazole (828), triforine
`(838), triphenyltin hydroxide (347), validamycin (846), vin
`clozolin (849), Zineb (855), Ziram (856), Zoxamide (857),
`1,1-bis(4-chlorophenyl)-2-ethoxyethanol (IUPAC-Name)
`(910), 2,4-dichlorophenyl benzenesulfonate (IUPAC-/
`Chemical Abstracts-Name) (1059), 2-fluoro-N-methyl-N-1-
`naphthylacetamide (IUPAC-Name) (1295), 4-chlorophenyl
`phenyl sulfone (IUPAC-Name) (981),
`a compound of formula B-5.1
`
`US 9,314,022 B2
`
`10
`a compound of formula B-5.4
`
`10
`
`15
`
`CF,
`
`O
`
`N1 O
`
`N
`
`F
`
`F
`
`(B-5.1)
`
`a compound of formula B-5.5
`
`25
`
`CH t
`Orcs
`
`C
`
`O
`
`o?y
`
`30
`
`(B-5.4)
`
`(B-5.5)
`
`a compound of formula B-5.2
`
`CH3
`
`N
`
`F
`
`F;
`
`N- N
`( N
`als 2
`N
`N
`
`C
`
`F
`
`a compound of formula B-5.3
`
`OCHF,
`
`N.
`
`O 1
`
`O
`
`35
`
`N
`
`F
`
`40
`
`(B-5.2)
`
`F
`
`a compound of formula B-5.6
`
`45
`
`50
`
`55
`
`CF,
`
`(B-5.3)
`
`60
`
`C
`
`C
`
`H
`N
`
`21
`
`Sa
`N
`
`C
`
`O
`
`65
`
`H3C
`
`N
`O1 n
`
`(B-5.6)
`
`th
`s' NH
`
`C
`
`

`

`11
`a compound of formula B-5.7
`
`US 9,314,022 B2
`
`12
`and a compound of formula B-7.2:
`
`(B-5.7)
`
`(B-7.2)
`
`10
`
`15
`
`25
`
`30
`
`35
`
`O
`CH3
`
`N
`M
`N
`
`Cl;
`
`N NH / \
`
`O
`
`2 2
`
`N
`
`H1 NCH,
`
`and (B8) glyphosate (419).
`It has been found that the use of component (B) in combi
`nation with component (A) Surprisingly and Substantially
`enhance the effectiveness of the latter against fungi, and vice
`versa. Additionally, the method of the invention is effective
`against a wider spectrum of Such fungi that can be combated
`with the active ingredients of this method, when used solely.
`A further aspect of the present invention is a method of
`controlling diseases on useful plants or on propagation mate
`rial thereof caused by phytopathogens, which comprises
`applying to the useful plants, the locus thereof or propagation
`material thereof a composition according to the invention.
`Preferred is a method, which comprises applying to the useful
`plants or to the locus thereof a composition according to the
`invention, more preferably to the useful plants. Further pre
`ferred is a method, which comprises applying to the propa
`gation material of the useful plants a composition according
`to the invention.
`The compounds of formula I occur in two different stere
`oisomers, which are described as the single enantiomers of
`formulae I, and I:
`
`40
`
`45
`
`Br
`3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic
`acid
`(2-bicyclopropyl-2-yl-phenyl)-amide
`(compound
`B-5.8), 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxy
`lic acid (9-isopropyp-1.2.3,4-tetrahydro-1,4-methano-naph
`thalen-5-yl)-amide (compound B-5.9), 1,3-dimethyl-5-
`fluoro-1H-pyrazole-4-carboxylic
`acid
`2-(1,3-
`dimethylbutyl)phenyl-amide
`(compound
`B-5.10),
`3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid
`(3',4'-dichloro-5-fluoro-1,1'-biphenyl-2-yl)-amide
`(com
`pound B-5.11), N-(2-3-chloro-5-(trifluoromethyl)pyridin
`2-yl)ethyl-2-(trifluoromethyl)benzamid
`(compound
`B-5.12),
`3-difluoromethyl-1-methyl-1H-pyrazole-4-car
`boxylic acid N-2-(1,1,2,2-tetrafluoroethoxy)phenyl-amide
`(compound B-5.13), 3-difluoromethyl-1-methyl-1H-pyra
`Zole-4-carboxylic acid N-2-(1,1,2,3,3,3-hexafluoropro
`poxy)phenyl-amide (compound B-5.14), 3-difluoromethyl
`1-methyl-1H-pyrazole-4-carboxylic acid N-2-(2-chloro-1,
`1.2-trifluoroethoxy)phenyl-amide (compound B-5.15),
`3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid
`N-(4-trifluoromethyl-biphen-2-yl)-amide
`(compound
`B-5.16),
`3-difluoromethyl-1-methyl-1H-pyrazole-4-car
`boxylic
`acid
`N-(2'-trifluoromethyl-biphen-2-yl)-amide
`(compound B-5.17) and 3-difluoromethyl-1-methyl-1H
`pyrazole-4-carboxylic acid N-(2'-trifluoromethyl-biphen-2-
`yl)-amide (compound B-5.18): (B6) a plant-bioregulator
`selected from the group consisting of acilbenzolar-5-methyl
`(6), chlormeduat chloride (137), ethephon (307), mepiduat
`chloride (509) and trinexapc-ethyl (841);
`(B7) an insecticide selected from the group consisting of
`abamectin (1), clothianidin (165), emamectin benzoate
`(291), imidacloprid (458), tefluthrin (769), thiamethoxam
`(792), a compound of formula B-7.1
`
`(B-7.1)
`
`O
`
`H3C
`
`Br
`
`Y.
`
`M
`N
`
`Cl;
`
`N NH / \
`
`O
`
`C
`
`N
`H1 NCH,
`
`50
`
`55
`
`O
`
`R
`
`|
`
`N
`N
`
`N
`V
`
`"
`
`CH
`
`O
`
`60
`
`R
`
`N
`
`65
`
`III
`
`

`

`13
`The invention covers all Such stereoisomers and mixtures
`thereof in any ratio. According to the invention “racemic
`compound of formula (I)” means a racemic mixture of com
`pounds of formula I and I.
`A preferred embodiment of the invention is represented by
`those compositions which comprise as component A) a com
`pound of formula (I), wherein R is difluoromethyl. Further
`preferred compounds of formula (I) are:
`3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid
`(9-dichloromethylidene-benzonorbornene-5-yl)amide
`(compound A-1.1): 3-difluoromethyl-1-methyl-1H-pyra
`Zole-4-carboxylic acid (9-difluoromethylidene-benzonor
`bornene-5-yl)amide (compound A-1.2); and
`3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid
`(9-dibromomethylidene-benzonorbornene-5-yl)amide
`(compound A-1.3).
`The designation of substituent X as chloro, fluoro or bromo
`means that both Substituents X have the same meanings.
`A preferred embodiment of the invention is represented by
`those compositions which comprise as component A) a com
`pound of formula (I), wherein R is trifluoromethyl. Further
`preferred compounds of formula (I) are:
`1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid
`(9-dichloromethylidene-benzonorbornene-5-yl)amide
`(compound A-1.4);
`1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid
`(9-difluoromethylidene-benzonorbornene-5-yl)amide
`(compound A-1.5); and
`1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid
`(9-dibromomethylidene-benzonorbornene-5-yl)amide
`(compound A-1.6).
`A further preferred embodiment of the invention is repre
`sented by those compositions which comprise as component
`B) a compound selected from azoxystrobin, picoxystrobin,
`fludioxonil, fempropidin, difenoconazole, cyprodinil, man
`35
`dipropamid, chlorothalonil, cyproconazole, epoxiconazole,
`propiconazole and epoxiconazole.
`Especially preferred compositions according to the inven
`tion comprise as component (A) a compound selected from
`3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid
`40
`(9-dichloromethylidene-benzonorbornene-5-yl)amide (com
`pound A-1.1) and 3-difluoromethyl-1-methyl-1H-pyrazole
`4-carboxylic acid (9-difluoromethylidene-benzonorbornene
`5-yl)amide (compound A-1.2), and as component (B) a
`compound selected from azoxystrobin, picoxystrobin, bix
`afen, fludioxonil, fempropidin, fenpropimorph, fluopyram,
`difenoconazole, tebuconazole, ipconazole, cyprodinil, man
`dipropamid, chlorothalonil, cyproconazole, prothioconazole,
`propiconazole and epoxiconazole.
`Further especially preferred compositions according to the
`invention comprise as component (A) the compound 3-dif
`
`14
`acid
`luoromethyl-1-methyl-1H-pyrazole-4-carboxylic
`(9-dichloromethylidene-benzonorbornene-5-yl)amide (com
`pound A-1.1) and as component (B) a compound selected
`from azoxystrobin, picoxystrobin, bixafen, fludioxonil, fen
`propidin, difenoconazole, cyprodinil, mandipropamid, chlo
`rothalonil, propiconazole, cyproconazole and epoxiconazole.
`Further especially preferred compositions according to the
`invention comprise as component (A) the compound 3-dif
`luoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (9-di
`fluoromethylidene-benzonorbornene-5-yl)amide
`(com
`pound A-1.2) and as component (B) a compound selected
`from azoxystrobin, picoxystrobin, fludioxonil, fenpropidin,
`fenpropimorph, fluopyram, difenoconazole, ipconazole, pro
`thioconazole, tebuconazole, cyprodinil, chlorothalonil.
`epoxiconazole, propiconazole, cyproconazole, and epoxi
`conazole.
`The compounds of formula (I) may be prepared as
`described below with reference to reaction Schemes 1 to 3.
`
`O
`Ha-( --
`OR
`
`Scheme 1
`
`X
`
`X
`
`--
`
`(II)
`
`NH2
`
`(III)
`
`X
`
`X
`
`O
`
`N N NH
`
`Het
`
`(I)
`
`Het is:
`
`R
`
`( \
`
`CH
`
`As shown in Scheme 1, a compound of formula (I), where
`R and Xareas defined above, may be synthesized by reacting
`a compound of formula (II), R is as defined above and R' is
`Cs alkyl, with an aniline of formula (III), where X is as
`defined above, in the presence of NaN(TMS) at -10°C. to
`ambient temperature, preferably in dry THF, as described by
`J. Wang et al. Synlett, 2001, 1485.
`
`US 9,314,022 B2
`
`10
`
`15
`
`25
`
`30
`
`45
`
`50
`
`Scheme 2
`
`X
`
`X
`
`-e-
`
`X
`o
`
`X
`
`O
`
`Ha-( --
`(II)
`
`OH
`
`NH2
`
`(III)
`
`

`

`15
`
`US 9,314,022 B2
`
`16
`
`—- i
`
`-continued
`+ (III) —
`
`Q
`(II")
`
`Alternatively, as shown in Scheme 2, a compound of for
`mula (I), where Het is as defined in scheme 1, R and X areas
`defined above, may be prepared by reacting a compound of
`formula (II), where Het is as defined above, with an aniline of
`formula (III), where X is as defined above, in the presence of
`an activating agent, such as BOP-CI (bis-(2-oxo-3-oxazolidi
`nyl)-phosphinic acid), and two equivalents of a base, such as
`triethylamine, in a solvent. Such as dichloromethane (as
`described, for example, by J. Cabré et al. Synthesis 1984,
`413) or by reacting a compound of formula (II"), where Het is
`as defined above and Q is chloro, fluoro or bromo, with an
`aniline of formula (III), where X is as defined above, in the
`presence of one equivalent of a base. Such as triethylamine or
`Sodium or potassium carbonate or bicarbonate, in a solvent,
`
`10
`
`15
`
`such as dichloromethane, ethyl acetate or N,N-dimethylfor
`mamide, preferably at -10 to 30°C. The compound of for
`mula (II") is obtained from a compound of formula (II) by
`treatment with a halogenating agent Such as thionyl chloride,
`thionyl bromide, oxalyl chloride, phosgene, SF/HF, DAST
`((diethylamino)sulphur trifluoride), or Deoxo-Fluor R (Ibis
`(2-methoxyethyl)aminosulphur trifluoride) in a solvent such
`as toluene, dichloromethane or acetonitrile.
`The compounds (II) and (II) are generally known com
`pounds and may be prepared as described in the chemical
`literature or obtained from commercial sources. The com
`pound (III) is a novel compound and may be prepared as
`described with reference to Scheme 3.
`
`Scheme 3
`
`NO
`
`COOH
`
`i-CHONO
`--as
`R
`it
`
`3.
`
`NH2 )-O
`
`R
`
`A
`
`NO
`
`B
`
`R
`
`R"
`
`-e-
`
`R
`
`it
`R
`
`NO
`
`C
`
`|
`
`CHNO2, piperdine
`
`6 H(F)
`
`F(H)
`
`-a-
`
`X
`
`X
`
`-a-
`
`O
`
`NO
`
`F
`
`NO
`
`NO
`
`N
`
`E
`
`|
`
`D
`
`|
`
`X
`
`o a
`
`X
`
`I
`
`I
`
`NH2
`
`(III)
`
`NO
`
`G
`
`

`

`US 9,314,022 B2
`
`18
`
`17
`As shown Scheme 3, the compound of formula (III) may be
`prepared by a Bechamp reduction or by other established
`methods, for example, by selective catalytic hydrogenation,
`of the nitro-compounds (E), (F) and (G).
`The 9-dihalomethylidene-5-nitro-benzonorbornenes (E),
`where X is chloro, bromo or fluoro, may be obtained by the
`Wittig olefination of the ketones (D) with in situ generated
`dihalomethylidene phosphoranes R"P=C(R)R, where
`R" is triphenyl, tri Ca. alkyl or tridimethylamine and X is
`halo, according to or by analogy with the procedures
`described by H.-D. Martin etal, Chem. Ber: 118,2514 (1985),
`S. Hayashi et al., Chem. Lett. 1979,983, or M. Suda, Tetra
`hedron Letters, 22, 1421 (1981).
`Compounds of formula (I) may be obtained as described in
`examples H1 to H7.
`
`S)=
`
`NO
`
`10
`
`15
`
`To a well stirred solution of isopentylnitrite (2.31 ml, 1.3
`eq.) in dimethoxyethane (50 ml) at 58° C. a mixture of 6-ni
`troanthranilic acid (2.76 g, 1 eq.) and 6,6-diethylfulvene (6.45
`g of 79% purity, 2.5 eq.) dissolved in 25ml dimethoxyethane
`was added dropwise within 8 minutes whilst the temperature
`rose to 67°C. After 30 minutes the dark reaction mixture was
`evaporated and purified on silica gel in hexane-ethyl acetate
`(20:1) to give 3.02 g (78%) of the desired product as an oil that
`solidified at room temperature (m.p. 60-61C.).
`
`EXAMPLE 3
`
`EXAMPLE1
`
`This Example illustrates the preparation of 9-(3-pentyl
`idene)-5-nitro-benzonorbornene:
`
`This Example illustrates the preparation of 1-methyl-3-
`trifluoromethyl-1H-pyrazole-4-carboxylic acid (9-dichlo
`romethylidene-benzonorbornene-5-yl)amide
`(compound
`A-1.4):
`
`25
`
`C
`
`C
`
`N
`
`O
`
`FC
`( \
`
`CH
`
`30
`
`35
`
`40
`
`45
`
`50
`
`(175
`9-Dichloromethylene-5-amino-benzonorbornene
`mg, 0.729 mmol, prepared as described in Example 6) in
`dichloromethane (10 ml) was reacted with 1-methyl-3-trif
`luoromethyl-1H-pyrazole-carboxylic acid (170 mg. 0.874
`mmol. 1.2 eq.) in the presence of bis-(2-oxo-3-oxazolidinyl)-
`phosphinic acid chloride (278 mg, 1.09 mmol. 1.5 eq.) and
`triethylamine (184 mg, 1.821 mmol. 2.5 eq.) at ambient tem
`perature under stirring for 23 hours. The reaction mixture was
`55
`extracted with saturated sodium bicarbonate solution and
`saturated brine, dried over NaSO and purified on silica gel
`in ethyl acetate-hexane-(1:1). 210 mg (69% of theory) of
`1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid
`(9-dichloromethylidene-benzonorbornene-5-yl)amide (com
`pound A-1.4 m.p. 179-181°C.) was obtained.
`
`60
`
`EXAMPLE 2
`
`This Example illustrates the preparation of 9-(3-pentyl
`idene)-5-nitro-benzonorbornadiene:
`
`65
`
`NO
`
`9-(3-pentylidene)-5-nitro-benzonorbornadiene (7.97 g
`prepared as described in Example 2) in THF (70 ml) was
`hydrogenated at 20° C. in the presence of Rh(PPh)Cl
`(Wilkinson's catalyst; 0.8 g). The reaction ceased after uptake
`of one equivalent of hydrogen.
`Evaporation and filtration of the crude on silica gel in ethyl
`acetate-hexane-(100:2) gave the desired product as an oil
`(7.90 g) that solidified on standing at room temperature (m.p.
`69-56° C).
`
`EXAMPLE 4
`
`This Example illustrates the preparation of 9-Oxo-5-nitro
`benzonorbornene
`
`NO
`
`9-(3-pentylidene)-5-nitro-benzonorbornene (7.0 g. 27.2
`mmol; prepared as described in Example 3) dissolved in
`dichloromethane