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 (11) Patent Number: KE 159 (45) Date of grant: 18/06/2003
(12) PATENT
(51) 1ntCL7:
A 01N 43/36, C 070 207/34, 401/12, 409/14
(21)    Application Number: 2001/ 000186
(22)    Filing Date: 11/11/2000
(30) Priority data:
9930750.6 29/12/1999 GB
(87) PCT details
WO/2001/049664    12/07/2001
 
(73)    Owner:
SYNGENTA PARTICIPATIONS AG, Schwazwaldalle 215,CH-4058 Basel, Switzerland
(72) Inventor:
TRAH, Stephan;
WALTER, Harald
SCHNEIDER, Hermann
(74)    Agent/address for correspondence: Hamilton Harrison & Mathews, P.O. Box 30333-00100,
Nairobi
 

 
(54) Title:
TRITWOROMETHYLPYRROLE CARBOXAMIDES AND TRIFL1JOROMETHYLPYRROLETHIOAMIDES AS FUNGICIDES
(57) Abstract:
Novel pyrrole derivatives of formula (I) wherein Xis oxygen or sulfur FQ,1? is hydrogen, C1,1?-Cz4?allcyl unsubstituted or substituted, or halogen; Ra? is CO7-C1,4?alkyl unsubstituted or substituted; and A is orthosubstituted aryl; orthosubstituted heteroaryl; bicycloaryl unsubstituted or substituted; or bicycloheteroaryl unsubstituted or substituted. The novel compounds have plant-protective properties and are suitable for protecting plants against infestations by phytopathogenic microorganisms.
 
 
- 1 -
Organic Compounds
The present invention relates to novel trifluoromethylpyrrolcarboxamides or trifluoromethylpyrrolthioamides which have microbicidal activity, in particular fungicidal activity. The invention also relates to the preparation of these substances, to agrochemical compositions which comprise at least one of the novel compounds as active ingredient, to the preparation of the compositions mentioned and to the use of the active ingredients or compositions in agriculture and horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
The trifluoromethylpyrrolcarboxamides of the present invention have the general formula I
 
wherein
Xis oxygen or sulfur,
R., is hydrogen, C1-C4alkyl unsubstituted or substituted, or halogen;
R, is C,-C4alkyl unsubstituted or substituted; and
A is orthosubstituted aryl; orthosubstituted hateroaryt; bicyctoaryl unsubstituted or substituted; or bicycloheteroaryl unsubstituted or substituted.
Surprisingly, it has now been found that the compounds of formula I exhibit improved biological properties which render them more suitable for the practical use in agriculture and horticulture.
Where asymmetrical carbon atoms are present in the compounds of formula I, these compounds are in optically active form. The invention relates to the pure isomers, such as enantiomers and diastereorners, as well as to all possible mixtures of isomers, e.g. mixtures of diastereomers, racemates or mixture of racemates.
 
-2-
Within the present specification alkyl denotes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl. Non-branched alkyl is preferred. Alkyl as part of other radicals such as alkoxy, haloalkyf, alkylcycloalkyl, alkylcycloalkoxy, etc. is understood in an analogous way. Halogen will be understood generally as meaning fluoro, chloro, bromo or iodo. Fluorq, chloro or bromo are preferred meanings. Halogen as part of other radicals such as haloalkyl, haloalkoxy, haloalkenyl, haloalkenyloxy, haloaryl or haloheteroaryl, etc. is understood in an analogous way. Haloaryl or haloheteroaryl designates mono- to five times halo-substituted aryl, whereby the halogens are independently chosen. Where more than two halogens are present, the halogens are preferably the same, e.g. trifluorophenyl, trichlorophenyl, tetrachlorophenyl or perchlorophenyl.
Cyckalkyl is, depending on the ring size, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.
Alkenyl will be understood as meaning straight-chain or branched alkenyl such as allyl, methallyi, 1-methylvinyl or but-2-enl-yl. Preferred alkenyl radicals contain 3 to 4 carbon atoms in the chain.
Alkynyl can likewise, in accordance with the number of carbon atoms, be straight-chain or branched and is typically propargyl, but-1-yn-1-yl or but-1-yn-3y1.
Aryl is phenyl, benzyl.
Heteroaryl will be understood as a 5- to 10-membered ring that may contain up to 3 heteroatoms, such as nitrogen, oxygen or sulfur. The following list of examples is not exhaustive : furyl, thienyl, imidazolyl, pyrazoiyi, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyrrolyl, dithiolyl, oxathiolyl, dioxazolyl, oxathiazolyl, oxathiolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazolyi, benzothiazolyl, benzoxazolyl,
isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyt, naphthyridinyl, isobenzofuranyl, isobenzazolyl, isoindazolyl, benzopyrrolyl, benzothiadiazolyl, benzisoxazolyl, purinyl.
 
-3-
Bicycloaryl or bicycloheteroaryt will be understood as a 6-membered aryl or 6-membered heteroaryl, wherein it may contain up to 3 heteroatoms such as nitrogen, oxygen or sulfur, and which is fused to an additional nag. The fused ring may be aromatic, partially hydrogenated or completely saturated, may be a ring from 5 to 7 ring members, of which up to 3 members may be heteroatoms selected from the group nitrogen, oxygen and sulfur. The following list of examples is not exhaustive: dihydroisobenzofuranyl, dihydroisoindotyl.
Within the group of compounds of formula I those compounds are preferred wherein : IR, is hydrogen, C,-Colkyl, C,C„haloalkyl,
C,C4haloalkoxy, C,-C4haloalkoxy-C,e.,alkyl or halogen ;
R2 is C,-C4alkyl, CI-C4haloalkyl, Ci-C4alkoxy-C,-C4alkyl or C,C.,haloalkoxy-C,-C4alkyl ; A is a group
cu
 
-4-
 

 
R7,
(A26)
124
R5    R7
o Ra
(A31)
R4
R6
(A32)
 
and
R, is C,-C-,cycloalkyl unsubstituted or mono- to trisubstituted by halogen, hydroxy, C,-C,alkoxy, C,-C4haloalkyl, C2-C,alkenyl. C2-C,arkynyl, C,-C,haloalkoxy or C,-C,alkyl; OcC,cycloalkenyl unsubstituted or mono- to trisubstituted by halogen, hydroxy,
C2-C4alkenyl, GrC4alkynyl, C-C,haloalkoxy or C,-C4alkyl; C„-C-,cyclodialkenyl unsubstituted or mono- to trisubstituted by halogen, hydroxy, C,-C,alkoxy, C-C4haloalkyl, C,C4alkenyl, C2-C4alicynyl, C-C,haloalkoxy or C,-C,alkyl; thienyl, furyl, pyrrolyl, pyrazolyl, oxazolyl, thrazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, imidazolyl, triazinyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyl, which are unsubstituted or substituted by halogen, C,C4haroalkyl, C-C4alkyl, hydroxy, cyano, nitro, CHO, C,-C4alkoxy-C,-C4alkyl. COOC,-C4alkyl,
C-C„haloalkoxy-C,-C4alkyl, C-Colkoxy or C1-C,,,haloalkoxy;
Re is C5-C,cydoalkyl, C,-C7cydoalkenyl or CrC7cydoalkadienyl which are unsubstituted or substituted by halogen, C-C,alkoxy, C-Colkoxy-C,Colkyl, C,-C,haloalkoxy-C,-C4arkyl, C1-C4allryl, C1-C4haloalkyl, C,-C4haloalkoxy. C2-C4alkenyl or C„-C,alkynyl; phenyl unsubstituted or substituted by halogen, C,-C,,alkoxy, C-C„haloalkoxy,
C,C4haloalkyl, CfC4alkenyl, CrC, alkynyl, CHO, COOC,-C,alkyl, C,C4alkoxy-C,-C4alkyl, C,-C4alkyl-C,-C4alkoxy, C,-C4haloalkoxy-C,-C4alkyl, cyano or nitro; thienyl, furyl, pyrrolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, thiadiazolyl,
triazinyl, pyridyl, pyridazinyl, pyrazinyl or pyrimidinyl, which are unsubstituted or substituted by halogen, C-C,haloalkyl,    hydroxy, cyano, nitro, CHO,
COOC,-C,alkyl,    C,-C4alkoxy-C,-C4alkyl, C,-C4alkoxy or
C,-C,haloalkoxy;
 
-5-
Rs, Rs, R7 and R. are identical or different and are each independently of the others hydrogen,    C,-C4haloalkyl or C,-C,haloalkoxy (subgroup AB1).
Within the subgroup AB1 are those compounds more preferred wherein
A is A1, A2, A3, A17, A20, A21, A24, A25, A26, A27 or A31;
is hydrogen or C,Csalkyl;
R, is C,-Csalkyl or C7-Csalkoxy-C,Csalkyl;
R, is cyclohexyi, cyciohexenyi or cydohexadienyl, which are unsubstituted or mono- to disubstituted by chloro, bromo,    C,Cshaloalkyl or CrCshaloalkoxy; thienyl, furyl,
triazinyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,C,alkyl, C,-C4haloalkyl or C,-C4haloalkoxy;
Rs, is cyclohexy1, cyclohexenyl or cyciohexadienyl, which are unsubstituted or substituted by halogen. C,-C„alkyl, C1-C4alkoxy, C1-C4haloalkyr or CI-C,haloarkoxy, thienyl, furyl, triazinyl, pyridyl, pyrazinyl, pylidazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-Colkyl, CrCshaioalkyl or C,C,haloalkoxy;
R., is hydrogen, halogen, C„-Csalicyl, C,-Cshaloaikyl, C,-Csalkoxy or Cceshaloalkoxy; and
Rs, Rs, R, and R„ are identical or different and are each independently of the others hydrogen or C„-Csalkyi (subgroup AB2).
Within the subgroup AC are those compounds preferred wherein
R, is hydrogen, C,-C,,alkyl or C,-CshaloalkYl;
R7 is C,-Csaikyl, C,-Cshaloalkyl or C.,-Csalkoxy-C,-Csalkyl;
A is A1, A2, A3, AS, A8, A10, A13, A14, A17, A18, A20, A21, A22, A24, A25, A26, A27, A29, A31 or A32;
Rs is C6C7cycloalkyl, unsubstituted or mono- to lrisubstttuted by halogen, hydroxy, Cs-C4alkenyl, Cs-C4alkynyl, C.,-Csalicyl or C,-Csalkoxy; Cs-C7cycloalkenyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, Cs-C4alkenyl, C2-C4alkynyl, C,-Csalicyl or C.,-Csalkoxy; Cs-Crcyciodialkenyl, unsubstituted or mono- to disubstituted by halogen, hydroxy, Cs-C,alkertyl, Cs-Cialkynyl, C,-Csalkyi or C.,-Csalkoxy; thienyl, furyl, isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyi, pyrimidinyt, pyrazinyl or pyridazinyl, which are unsubstituted or substituted by halogen, hydroxy,    CI-Cshaloaficyl, CrCsafkoxy or
C1-C4haloalkoxy;
 
19.    (Amended) The crystallization process of Claim 1, wherein [the] p amount of solids
in the solution in the form of agglomerates and/or aggregates is maintained at about 10% by weight or less of the total solids of the compound in the solution.
25.    (Amended) The process of Claim 23, wherein [the] a particle size of the feedstreara is less than [the] a particle size of the seed crystals after growth on the seed crystals.
26.    (Amended) The process of Claim 23, wherein [the] a range of [the] A particle size of the seed crystals is not greater than about 3 standard sieve sizes.
27.    (Amended) The process of Claim 23, wherein [the] A particle size of the feedstream is less than about 150 mesh.
28.    (Amended) Theprocess of Claim 23, wherein [the] a particle size ofthe seed crystals
is from about 100 mesh to about 150 mesh.
31.    (Amended) The process of Claim 23, wherein the amount of [solids] egy..,to in the
solution formedby [primary and/or secondary] nucleation [in the crystallizerl is maintained at about 20% by weight or less of the total solids of the compound in the solution.
REM
Claims 2, 5, 9 through 12 17 through 19, 25 through 28, and 31have been amended. No new matter has, been added by these amendments. Applicants have amended Claim 2 to correct the Markush language in the claim. Applicants have amended Claim 5 to more clearly delineate the crystal structures referred to in the claim Applicants have amended Claims 9 through 12 and 24 through 28 to correct the antecedent basis of the phrase "this particle size" in the places where this phrase is located in these claims. Applicants have amended Claims 17 through 19 to correct the antecedent bases for the phrase "the amount of solids." Applicants have amended Claim 31 to correct the antecedent basis of the phrase "the crystallizer" where that phrase occurs in the claim.
 
Applicants have also amended the claim to address the objection of what applicants mean by primary or secondary nucleation.
The claim changes described above are believed to be unrelated to any statutory requirement for patentability, but are deemed worthwhile to make the claim language more readable. Applicants note that no prior art has been cited to require the changes identified above and the changes have been made to clear up matters of form only. As required, Applicant is enclosing the amended claims on substitute pages 28-32 to replace the claims currently on file. Additionally, a substitute page 33 with the Abstract is also enclosed.
The Examiner indicates that Claims 1 through 37 meet the novelty and industrial applicability requirements under PCf Articles 33(2) and 33(4). The Examiner asserts that Claims 1 through 37 do not meet the inventive step requirement under PCT Article 33(3). In particular, the Examiner has taken the position that Claims 1 through 37 lack an inventive step under PCT Article 33(3) as being obvious over Grott in view of Port.
Withparticular respect to Claim I, Grott '123 does not disclose or teach the claimed process because Gran '123 does not disclose the creation of a supersaturated solution to the supersaturation level of 5 g/1 claimed in Claim 1. Indeed, Grott '123 only teaches that the ground salt is added to a substantially saturated saturation, and mentions that localized supersaturation occurs when ground crystals are added to the saturated solution. Grott '123 also does not disclose achieving any amount of supersaturation, e.g. 5 g/I, as does the claimed invention. The amount of supersaturation, as discussed in detail in the present specification in the Detailed Description of the Invention at least at page 4, lines 3 through 9, was a surprising discovery, given the amount of supersaturation that could be achieved and the stability of the resultant solution. Thus, Grott '123 does not teach a claimed element of the invention. Since Grott '123 does not teach an element of the claimed
 
invention, the remaining reference, Port '848, must then teach this element in order for the
combination to teach all of the claimed elements of the present invention. However, Port '848 also
does not teach the creation of a supersaturated solution of at least 5 WI. Thus, the combination of
the references lacks at least one element of Claim 1. Since Claims 2 through 22 depend from non-
obvious Claim 1, Claims 2 through 22 should be deemed non-obvious as well. Thus, Applicants
request that the Examiner withdraw the rejection of Claims 1 through 22 under PCT Article 33(3).
Moreover, the recitation of a supersaturation level of at least about 5 g/l is not an obvious
variation of the cited Grott '123 and Port '848 references. Those skilled in the art would not operate
a crystallization process under conditions sufficient to create supersaturation of at least about 5g/I
because, not knowing the high supersaturation capacity, one skilled in the art would expect juch
conditions to exceed the supersaturation capacity. By exceeding the supersaturation capacity, one
skilled in the art would expect uncontrolled precipitation of solid product rather than controlled
productive growth of large crystals. Therefore, a skilled artisan would not modify the references to
use conditions to create at least 5g/I supersaturation because of expected adverse consequences.
With particular respect to Claim 23, the combination of Grott '123 and Port '848 does not
disclose or teach the claimed process for the same reason as identified above for Claim I.
Additionally, the combination does not teach the claimed invention because neither Grott '123 nor
Port '848 teaches the high degree of agitation required by the claimed invention. Claim 23 requires
agitation of the solution at an agitation index of at least 4. As discussed in the specification, an
agitation index of at least 4 requires that the mixture have a turnover of slurry, but does not require
that all solids be held in suspension. Grott '123, in fact, discloses only that, in Example 1, the
containers were shaken after a one (1) month period had passed. Grott '123 also refers to the
 
agitation that takes place as being "modest agitation," unlike the agitation required by the claimed invention.
Grott '123 also does not disclose the feed rate of the claimed invention. The Examiner states that the choice of the feed rate is optimized to reach a desired supersaturation level of the solution. This statement assumes that one skilled in the art would know what a "desired" level of supersaturation is. However, in this case the "desired" or claimed supersaturation level of 5 g/1 is not recognized by those skilled in the art to be desired, as discussed in detail above. The feed rate of the claimed invention depends on many process parameters. Also, the claimed invention delineates an unustally high feed rate, e. g. 100 g/l/min. The conventional thinking regarding growth of crystals is that long residence times, low feed rates and low growth rates are ideal. The claimed invention goes against this conventional thinking. One skilled in the art would not utilize a feed rate this high because, before the advent of the present invention, one skilled in the art would have assumed that such a high feed rate would exceed the supersataration capacity and create an uncontrolled nucleation of crystals resulting in small particles rather than the desired controlled growth of large, desirable crystals. It is important to note that no feed rate is specified in Grott '123 reference; however, it must be remembered that Grott '123 does not teach a supersaturated solution like that of the claimed invention and, likewise, does not disclose a desired feed rate to achieve this supersaturation level. Indeed, Grott '123 could not use a feed rate such as that claimed herein, because Grott '123 teaches that the solution must be left untouched in order to grow the crystals. For example, Grott '123 teaches, at Column 6, lines 14 through 26, that the solution is created and then left exposed to the desert sun for two months. Thus, Grott '123 practices the conventional thinking regarding the controlled growth of crystals and teaches the opposite of the claimed invention.
 
as argued above, is not described in either the Grott '123 or the Port '848 references. Thus, the rejection of Claim 35 cannot stand. Since Claims 36 and 37 depend from non-obvious claim 35, Claims 36 and 37 should be deemed non-obvious as well. Accordingly, Applicants request that the Examiner withdraw the rejection of Claims 35 through 37 under PCT Article 33(3).
In addition to the above arguments that the combination of the references does not make obvious the claimed invention, Applicants submit that these two references should not be combined because the references teach not combining the references. For example, if the Port '848 invention were operated at the operating temperatures described in Grott '123, Port '848 would not operate in its intended manner. The range of operating temperatures disclosed in Port '848 is from 36 to 109 degrees Celsius, whereas the range of operating temperatures disclosed in Grott '123 is from 400 to 500 degrees Fahrenheit, which converts to a range of approximately 204 to 260 degrees Celsius. Further, Port '848 specifically distinguishes its invention from higher operating temperature prior art references, such as U.S. Patent Nos. 2,962,348 and 3,131,996. See, Column 1, lines 41 through 60. Thus, Port '848 actually teaches away from the combination of Port '848 and Grott '123, as suggested by the Examiner. In addition, the Grott '123 reference discloses that the invention is distinguished from those previous inventions that utilize convention vacuum pan processing, open or closed pan evaporators. See, Column 2, lines 55 through 60 and Column 4, lines 1 through 5. However, the Port '123 reference specifically teaches that a vacuum is applied to the process through line 183. See, Column 5, lines 51 through 60. See also, Column 8, lines 27 through 30. Hence, Grott '123 actually teaches away from the combination with Port '848 suggested by the Examiner. Thus, the combination of these two references is improper. Applicants request that the Examiner withdraw the rejection of Claims 1 through 37 under PCT Article 33(3) based upon the
 
combination of Grott '123 and Port IA& Applicants sun= mat none of me roregoing reverences, alone or in any combination, obviate the invention as claimed in Claims 1 through 37.
In view of the foregoing amendments and remarks, Applicants request reconsideration ofthe present application and allowance of Claims 1 through 37. The examiner is invited to contact the undersigned representative if the Examiner believes that this would expedite prosecution of the present application. Applicants further request that the Examiner withdraw the objections to the claims and the citation of Grott in view of Port with respect to Claims 1-37. It is not believed that any fees are owed with respect to this response; however, any fees which may be necessary can be charged to Deposit Account No. 19-1970.
 
R, is hydrogen, cyano, nitro, halogen, C.,-C,,alkm, C,-C,haloalkyl, C,-C4alkyl, C,-C,alkoxy-C,-C4alkyl, C,-C,haloalkoxy-C,-C,alkyl or C,-C4haloalkoxY;
R5, R$, R,, R8 and R$ are identical or different and are each independently of the others hydrogen, halogen, C.,-C,haloalkyl, C,-C,alkyl, C,e,haloalkoxy-C,-C,alkyl, C,C,alkoxy, C,-C,haloalkoxy, C.,-C,alkoxy-C,-C,alkyl or CrC7cycloallryf (subgroup AA).
Within the group M of compounds of formula I those compounds are preferred wherein X is oxygen (subgroup AB).
Another group of compounds of formula I within the group M are those wherein Xis sulfur (subgroup AC).
Within the subgroup AB are those compounds preferred wherein
R., is hydrogen, C,-C,alkyf or C1-C4haloalkyl;
Rr is C.,-C,alkyl, CrG3hafoalkyl or C1-C5alkoxy-C,-05alkyl;
A is Al, AZ A3, AS, A8, A10, A13, A14, A17, A18, A20, A21, A22, A24, A25, A26, A27, A29, A31 or A32;
R, is CrC7cycloafkyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, C2-C4alkenyl, C2-C,alkynyl, Cl-C$alkyl or C1-C,alkoxy; CrGrcycloalkenyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, CrC4alkenyl, Cr C4aikynyl, C1-C,alkyl or CrCAlkoxy; C.-C-pcyclodialkenyl, unsubstituted or mono- to disubstituted by halogen, hydroxy, C2-C4alkenyl,    CrCsalkyl or C1-C3alkoxy;thienyl, furyl, isoxazolyl,
oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, which are unsubstituted or substituted by halogen, hydroxy, C,-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy or C.,-C4haloalkoxy;
R„ is Crqcycloalkyl, C5-C,cycloalkenyl or CrC-icycloaltadienyl, which are unsubstituted or substituted by halogen, Ci-C4alkyl, C1-C4alkoxy, C2-C4alkenyl, CrC,alkynyl, C,C,haloalkyl or C,-C4haloalkoxy; phenyl which is unsubstituted or substituted by halogen, C.,-C„afkyl. CrC4alkoxy, CrC4haloallryl or CrC„haloalkoxy; thienyl, furyl, isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl which are unsubstituted or substituted by halogen, C,-C,allryl, C1-C4alkoxy, C1-C4haloalkyl or C1-C4haloalkoxy;
R, is hydrogen, halogen, C.,-C,alkyl, CrC,alkoxy, C1-C4haloalkyl or C,-C4haloalkoxy; and
 
        - 13 -   
Scheme 1         1)Tosmic/base
-20° to reflux        F3C,    COO-C,-C4alkyl
    coo-c,-05-alkyl    fLeaving group)   

OH /H20    F3C    COOH
0° - reftux
Route 2 (Trifluoroacetoacetic acid-route, analogous to JP-07157466) Scheme 2
1) HC(OMe)3 or HC(OEt)3 0    0
F3C    OC,-Corkyl    Acz0    F0C 1j OC,Calkyl
 

 
Base 1 / H20/Meal-f or VON    F5C     
or isopropanol/tHF 0' - reflux       
 
-14-
R,, is C5-C,cycloalkyl, C5-C,cycloalkenyl or C5-C,cydoakadienyr, which are unsubstituted or substituted by halogen, C,-C,alkyl, C.,-C,alkoxy, C„-C,alkenyl, C,-C,allrynyl, C,-C4haloalkyl or CriC,haloalkoxy; phenyl which is unsubstituted or substituted by halogen, C,-C,alkyl,
C,C,haloalicyl or C,-C„haloalkoxy; thienyl, furyl, isoxazolyi, oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl which are unsubstituted or substituted by halogen, CI-C,alkyl, C,-C,alkoxy, C,-C„haloarkyl or C,-C4haloalkoxy;
R„ is hydrogen, halogen, C.,-C4alkyl, C,C,alkoxy, C,-C4haloalkyl or C,-C,haloalkoxy; and R5, R5, R, and R„ are identical or different and are each independently of the others hydrogen. C,-C4alkyl, C,C4alkoxy, C,C,haloalkyl or C,-C,haloalkoicy (subgroup AC1).
Within the subgroup AC1 are those compounds more preferred wherein
A is Al, A2, A3, A17, A20, A21, A24, A25, A26, A27 or A31;
R, is hydrogen or Cl-C.,alkyr;
R, is 0,-C,alkyl or C,-Cralkoxy-C,-C,alkyl;
R, is cyclohexyl, cydohexenyl or cyclohexadienyl, which are unsubstituted or mono- to disubstituted by chloro, bromo,    Cl-C,haloalkyl or C.,-C,haloalkoxy; thienyl, furyl,
triazinyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-C,allryl, C.,-C,haloalkyl or C1-C4haloalkoxy;
R,„ is cyclohexyl, cydohexenyl or cydohexadienyl, which are unsubstituted or substituted by halogen, C,-C4alkyl, Cr C,alkoxy, C,-C,haloalkyl or C,-C,haloalkoxy; thienyl, furyl,
pyridyl, pyrazinyl, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-C4alkyl, C1-C,haloailryl or C1-C4haloalkoXy;
R, is hydrogen, halogen, Cra,alkyl,    C,C,afkoxy or C,-C3haloalkoxy; and
R5, R5, R, and t4, are identical or different and are each independently of the others hydrogen or C,-C,alkyr (subgroup AC2).
The compounds according to formula I may be prepared according to the following reaction schemes.
A) Synthesis of he pyrrole carboxylic acids :
Route 1 (Tosmic-route)
 
-15-
Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.
The following non-limiting examples illustrate the above-described invention in more detail. Temperatures are given in degrees Celsius. The following abbreviations are used:
m.p.= melting point; b.p.= boiling point. "NMR" means nuclear magnetic resonance spectrum. MS stands for mass spectrum. "%" is percent by weight, unless corresponding concentrations are indicated in other units.
Example 1: 1-Methyl-4-tritluoromethy1-1H-pyrrole-3-carboxylic acid 14-(4'-chloropttenyl)- pyridin-3-yijamide
a) 1-Methyl-4-trifluoromethylpyrrol-3-carboxylic acid
F„C„    OH
CH,
Sodium hydride (8.11 g of a 75% dispersion in oil) is suspended at +5°C in a mixture of DMSO (300 ml) and diethylether (100 mr). A solution of ethyl 4,4,4-trifluorocrotonate (20 g) and TOSMIC (23 g) in DMSO (100 ml) is added through a dropping funnel at such a rate that the temperature does not exceed 10°C. After stirring the reaction mixture for an additional hour at Mal temperature methyl iodide (15.6 ml) is added with cooling. After 2 hours at room temperature the reaction mixture is poured onto crushed ice. Repeated extraction with ether, washing of the combined organic phases with brine and evaporation of the solvent under reduced pressure gives a product mixture in form of a light amber oil. The crude product mixture is heated at 60°C in a mixture of ethanol (100 ml) and sodium hydroxide (50 mi of a 30% aqueous solution). Washing of the solution with ether, acidifying of the aqueous phase with concentrated hydrochloric acid and filtering gives the 1-methyl-4-trifluoromethylpyrrol-3- carboxylic acid in form of a crystalline solid. 1H-NMR (CDCI,): 7.24(d,1H); 6.88(d,11-1); 3.63(s,3H).
In analogous manner the new compounds 1-ethyl- (m.p.146-148°C) and 1-mettioxyrnethyl-4- trifluoromethylpyrrol-3-carboxylic acid can be prepared.
 
-16-
 

 
Base 1 = NaHCO3, Na2CO3, KHOO, K2CO3, CaCO3 and other bases Base 2 = NaOH, KOH, Nati, KH, n-BuLi and others
B)    Synthesis of the amides/thioamides Scheme 3
C)    Synthesis of the ortho-substituted amines A-NH2:
The compounds are either known from the literature or can be prepared by known methods. For example the following amines or important intermediates for the synthesis of the amines can be prepared according to the following literature:
A,-NHz : Tetrahedron 1993,49,49-64 or EP-83975 or J,Org.Chem. 1995,60,292; A2-NH2: EP-737682;
A3-NH2 : J.Chem.Res.(S) 1978,11,428 or Chem.Scr.1972,2,245;
AiT-NH2: Org.Prep.Procedures Int. 1989,21,141;
A2,-NI-12: J.Chem.Soc.Perkin 11981,5,1591;
Az-MHz ; Tetrahedron 1993,49,49-64 or Heterocycles 1999,51,721;
A2,-N112 : Synthesis 1996.10,1015 or Synthesis 1994,9,931;
 
- 17 -
c) 1-Methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid (4-(4.-chroropheny1)-pyridin-3- yllamide
F,C    NH    [cmpd. 6.10]
tJ CH,
A solution of 0.54 g (2,8 mmol) 1-methyl-4-triftuoromethylpyrrol-3-carboxylic acid and 0.39 g (3.1 mmol) oxalyl chloride in 20 ml methylene chloride is stirred for 2 hours at room temperature in the presence of a catalytic amount of DMF. Then the acid chloride solution is slowly added to a solution of 0.57 g (2.8 mmol) 3-amino-4-(4'-chloraphenyi)pyridine, 0.34 g (3.4 mmol) triethylamine and 15 ml methylene chloride. The resulting mixture is then stirred for 16 hours at room temperature. After the addition of ethylacetate, the organic phase is washed twice with water. After drying the organic phase over sodium sulfate, the solvent is removed in a water jet vacuum. The obtained crude product is purified by column chromatography over silica get (eluant: hexaneTTHF 1:3). Yield: 0.4 g 1-methy1-4- trifluoromethyl-1H-pyrrole-3-carboxylic add [4-(4'-chloropheny1)-pyridin-3-yflamide in the form of yellowish crystals; m.p. : 178-16(1°C.
The following compounds are prepared in a similar way, using analogous methods.
 
- 18 -
b)4-(4'-chloropheny1)-3-nitropyridine
N \    CI
NO2
In a sulfonation flask 6.9 g (44 mmol) of 4chforo-3-nitropyridine, 6.5 g (42 mmcl) 4-chloro¬phenylboronic acid, 6.0 g (44 mmcl) potassium carbonate (saturated solution in water) and 1.0 g (0.9 mmol) tetrakia(triphenylphosphine)palladium are dissolved in 100 ml of dimethoxyethane (DME). The mixture is heated under reflux conditions under a constant nitrogen stream for 5 hours. Then the solvent is removed in a water jet vacuum and the residue taken up in ethylacetate. The organic phase is washed twice with water and after drying of the organic phase with sodium sulfate, the solvent is removed in a water jet vacuum. The resulting crude product is purified by column chromatography over silica gel (eluant: hexane/ethylacetate 1:1). Yield: 8.9 g 4-(4'-chloropheny1)-3-nitropyridine in the form of brownish crystals; m.p. 74-76°C.
c) 3-amino-4-(4'-chlorophenyl)pyridine
N    CI
NH2
In a sulfonation flask 8.4 g (36 mmol) 4-(4'-chlorophenyl)-3-nitropyridine is dissolved in a mixture of 100 ml water, 35 mi acetic acid and 10 ml n-propanol. After the addition of 7.0 g (125 mmol) iron powder, the mixture is heated for 3 hours under reflux conditions. After cooling to room temperature the mixture is diluted with ethylacetate and filtered over hyflo. Then the filtrate is neutralized by the addition of sodiumbicarbonate solution and the organic phase separated. The water phase is extracted twice with ethylacetate and the combined organic phases dried over sodium sulfate. After distilling off the solvent in a water jet vacuum the obtained raw material is purified by column chromatography over silica gel (eluant: ethylacetate). Yield: 3.9 g 3-amino-4-(4'-chlorophenyl)pyridine in the form of a slightly brownish powder; m.p. : 144-146°C.
 
-19-
1.14    H    CH,    0        H   
1.15        CI-I,    0        H    resin
1.16    H    CH,                resin
1.17    CH,    CH,    0           
1.18    H    CH2OCH,    0        H   
1.19        CH,    o    Ali    H   
1.20        CH,    0    i    H   
1,21        CH,    0           
1.22    H    CH,    0        H   
1.23    H    CH,    0        H   
1.24    H    CH,    0    cif    H    182-85
1.25    H    CH2OCH,    0    F. if    H    171-73
1.26    H    CH,    0        H    132-34
1.27    H    CH2OCH,    0        H   
1.28    H    CH,    0    'o    H   
1.29    H    CH,               
 
-20-
Table 1:    Rt H H H
H
H
H
H H H H H
H
H    Compounds of the formula I, wherein A = Al R4
R2    X    IR,
CH,    0    "50
CH,    0
CH3    0
5,9
CH,    0
5,P
CH,    0
—CS
CH,    0
—dr
CH3    0
0
CH,    0
CH,    0
—0—er
CH,    0
CH,    0
CH,CH,    0
CH3    S    IR,
H
H
H    Phys. Data
[m.p. °C]
Compd. No.
1.1
1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10
1.11
1.12
1.13               
 

 

 
-23-
 
2.7    H    CH,    0
2.8    H    CH,    0
2.9    H    CH3    0
2.10    H    CH3    0
2.11    H    CH,    0
2.12    H    CH3    0
2.13    H    CH,    S
2.14    H    CH,    0
2.15    H    CH,    S
2.16    H    CH,    0
2.17    CH,    CH3    0
2.18    H    CH2OCH,    0
2.19    H    CH,    0
2.20    H    CH,    0
2.21    H    CH,    0
 
H
-0 H
_0„... H
a _. H
.
-    -OC: H
 H
_o_at, H
 H
_0,, H
-    H
50 H &-c' H
 
 
-25-
1.60    H    CH,    0
")-di
1.61    H    CH,    0
—0
1.62    H    CH,    0
1.63    H    CH,    0
—CC H
1.64    H    CH,    0    i0-' H
1.65    CH,    CH,    0
H
O
Table 2:    Compounds of the formula I, wherein A = A2 =
— - - F
Compd.    R,    R2    X    R,    H4    Phys. Data
No.    Imp- °C]
2.1    H    CH,    0    "50    H
2.2    H    CH,    0    ci)0    H
2.3    H    CH,    0
52 H
2.4    H    CH,    0
5.$1)    H
2.5    H    CH,    0
-    d H
2.6    H    CH2OCH3 0
-    d H
 
-26 -

2.37    H    CH,    0
2.38    H    CH,    0
2.39    H    CH,    0
2.40    H    CH,    0
2.41    H    CH2OCH,    0
2.42    H    CH,    0
2.43    H    CH,    S
2.44    H    CH,    0
2.45    H    CH,    0
2.46    H    CH2OCH,    0-
2.47    H    CH,    0
2.48    H    CH,    0
2.49    H    CH,    0
2.50    H    CH2OCH,    0
2.51    H    CH,    0
 

 
-28 -
Table 3:    Compounds of the formula i, wherein A = A17 =
 
Compd.    R.,    R,    X    R„    R4    Phys. Data
No.                        [m•p• °C]
3.1    H    CH,    0    -0       
3.2    H    CH,    0        H   
3.3    H    CH,    0        H   
3.4    H    CH,    0        H   
3.5    H    CH2OCH,               
            0           
3.8    H    CH,               
            0           
3.7    H    CH,            H   
3.8    H    CH,            H   
3.9    H    CH,    0        H   
3.10    H    CH,    0        H   
3.11    H    CH,CH,    0        H   
 
-29-
 
2.52    H    CH3    0
2.53    H    CH2CH3    0
2.54    H    CH3    0
2.55        CH3    0
2.56        CH3    0
2.57    CHs    CH3    0
2.58    H    CH3    0
2.59    H    CH3    0
2.60    H    CH3    0
2.61    H    CH2CH3    0
2.62        CH3    0
2.63    H    CH3    0
2.64    H    CH3    0
2.65    H    CH3    0
2.66    H    CH3    0
2.67    CH3    CH3    0
 
H
o. H
H
H
H
H
H
H
H
11-N
 
 
- 30 -
 
Table 4:    Compounds of the font-Lb I, wherein A = A21
N.,s
 

Compd.    R,    R,    X
No.       
4,1    H    CH3    0
4.2    H    CH,    0
4,3    H    CH,    0
4.4    H    CH,    0
4.5    H    CH2OCH3
        0
4.8    H    CH,
0
4.7    H    CH3    0
4.8    H    CH3    0
4.9    H    CH3    0
4.10        CH,    0
4.11    H    CH2CH3    0
4.12    H    CH,
 
-31-

3.12    H    CHa    0
3.13    H    CH,    0
3.14    H    CH,    0
3.15    H    CH,    0
3.16    H    CH,    0
3.17    H    CH,   
            0
3.18    H    CH,   
            0
3.19    H    CH,   
            o
3.20    H    CH,   
            0
3.21    H        CH,"
.
3.22    H    CH,    0
3.23    CH,    CH,   
            0
3.24    H    CH,    .
3.25    H    CHa    S
           
 
- 33 -
 
Table 5:    Compounds of the formula i, wherein A = A24
Ft,
 
4.13    H    CH,    0    cs
4.14    H    CH,    0   
4,    H    CH,    0   
4.16    H    CH,    0   
4.17    H    CH,    0   
4.18    H    CH$    0    —Usk,
4.10    H    CH,    0   
4.20    H    CH$    0   
4.21    H    011a    0   
4.22    H    CH,    0   
4.23    CH,    CH,    0   
4.24    H    CH,       
4.25    H    CH,       
 
- 35 -
Table 6:    Compounds of formula I, wherein A = A25 =
 
Compd.    R,    R2    X    R31    R,    Phys. Data
No.                        [m•p. °C]
6.1    H    CH,    0        H   
6.2    H    CH,    0        H   
6.3    H    CH,    0        H   
6.4    H    CH,    0        H   
6.5    H    CH2OCH,            H   
            0           
6.6    H    CH,            H    
            0           
6.7    H    CH,    0        H   
6.8    H    CH,            H   
6.9    H    CH,    0        H   
6.10    H    CH,    0        H    178-180
6.11    H    CH2CH,    0        H   
6.12    H    CH2OCH,    0        H   
 

    5.13    I-I    CH3    0       
    5.14    H    CH,    0       
    5.15    H    CH,    0       
    5.16    H    CH,    0       
    5.17    H    CH,       
            0
    5.18    H    CH,         0
    5.19    H    CH,       
            0
    5,20    H    CH,       
           
    5,21    H    CH,       
            0
    5.22    H    CH,       
            O
    5.23    CH,    CH,    0       
    5.24    H    CH,    0       
    525    H    CH,       
 
6.29    H    CH,   
            O
6.30    H    CH,    O
6.31    CH,    CH,    O
6.32    H    CH,    0
6.33    H    CH,    S
6.34    H    CH,    O
6.35    H    CH,    O
 

 
-39 -
7.13    H    CH,    0    —P    H
7.14    H    CH,    0    H
7.15    H    CH,    0    ci    H
Table 8:    Compounds of the formula I, wherein A = A27 =
 

        —N    R4
Compd.    IR,    R2    X
No.           
8.1    H    CH,    0
8.2    H    CH,    0
8.3    H    CH2CH,    0
8.4    H    CH2OCH3    0
8.5    H    CH,    .0
8.6    H    CH2OCH3    0
8.7    H    CH,    S
8.8    H    CH,    0
 
-40 -
Table 7:    Compounds of the formula I, wherein A = A26 =
N-

Compd. No.    R,            R4
7.1    H    CH,    0    H
7.2    H    CH,    0    a    H
7,3    H    CH,CH,    0    _C yo H
7.4    H    CH2OCH,    0    p    H
7.5    H    CH,    0    H
7.6    H    CH2OCH,    0    H
7,7    H    CH,    S    H
7.8    1-1    CH,    0    H
7.9    H    CH,    0   
7.10    CH,    CH,    0    H
7.11    H    CH,    0    H
7.12    H    CH,    0   
 
-41 -
Table 9:    Compounds of the formula I, wherein A = A31 =
   

 
Compd.    R,    Rz    X    Ft,    RS    Re    R,    R,    phys.data
No.                                    m.p.
9.1    H    CH,    0    H    H    CH,    CH,    CH,   
9.2    H    CH,CH,    0    H    H    CH,    CH,    CH,   
9.3    H    CH2OCH,    0    H    H    CH,    CH,    CH,   
9.4    CH,    CH,    0    H    H    CH,    CH,    CH,   
9.5    H    CH,    S    H    H    CH,    CH,    CH,   
9.6    H    CH,    0    H    CH,    CH,    CH,    H   
9.7    H    CH2OCH,    0    H    CH,    CH,    CH,    H   
 
-42 -
 

3.9    H    CH,    0
8.10    CH,    CH,    0
8.11    H    CH,    0
8.12    H    CH,    0
8.13    H    CH,    0
8.14    H    CH,    0
8.15    H    CH2OCH,    0
8.16    H    CH,    0
8.17    H    CH,    0
8.18    H    CH,    0
 
-43-
Example 2-5: Action against Pyrenophora Ceres !barley (Net blotch on barley)
1 week old barley plants cv. Express are treated with the formulated test compound (0.002% active ingredient) in a spray chamber. Two days after application barley plants are inoculated by spraying a spore suspension (3 x 10. conidialmi) on the test plants. After an incubation period of 2 days at 20° C and 95% r. h. plants are kept for 2 days at 20° C and 60% r.h. in a greenhouse. The disease incidence is assessed 4 days after inoculation. Compounds of Tables 1 to 9 show good activity in this test.
Example 2-9: Action against Septoria nodorum /wheat (Septoria leaf spot on wheat) 1 week old wheat plants cv. Anna are treated with the formulated test compound
(0.02% active ingredient) in a spray chamber. One day after application wheat plants are inoculated by spraying a spore suspension (5 x 105 conidia/ml) on the test plants. After an incubation period of 1 day at 20° C and 95% r. h. plants are kept for 10 days at 20° C and 60% r.h. in a greenhouse. The disease incidence is assessed 11 days after inoculation. Compounds of Tables 1 to 9 show good activity in this test.
 
-44-
Formulation Examples for compounds of formula I
Working procedures for preparing formulations of the compounds of formula I such as Emulsifiable concentrates, Solutions, Granulates, Dusts and Wettable powders are described in WO 97/33890.
Biological Examples: Fungicidal actions
Example B-1: Action against Puccinia recondite /wheat (Brownrust on wheat)
1 week old wheat plants cv. Anna are treated with the formulated test compound
(0.02% active ingredient) in a spray chamber. One day after application wheat plants are inoculated by spraying a spore suspension (1 x 10' uredosporeslml) on the test plants. After an incubation period of 2 days at 20° C and 95% r. h. plants are kept in a greenhouse for 8 days at 20°C and 60% r.h. The disease incidence is assessed 10 days after inoculation. Compounds of Tables 1 to 9 show good activity in these tests (< 20% infestation).
Example B-2: Action against Podosphaera leucotricha apple (Powdery mildew on apple) 5 week old apple seedlings cv. McIntosh are treated with the formulated test compound (0.002% active ingredient) in a spray chamber. One day after application apple plants are
inoculated by shaking plants infected with apple powdery mildew above the test plants. After an incubation period of 12 days at 22° C and 60% r. h. under a light regime of 14/10 h (light/dark) the disease incidence is assessed.
Compounds of Tables 1 to 9 show good activity in this test.
Example B-3: Action against Venturia inaequalis apple (Scab on apple)
4 week old apple seedlings cv. McIntosh are treated with the formulated test compound (0.02% active ingredient) in a spray chamber. One day after application apple plants are inoculated by spraying a spore suspension (4 x 10' conidia/ml) on the test plants. After an incubation period of 4 days at 21° C and 95% r. h. the plants are placed for 4 days at 21° C and 60% r. h. in a greenhouse. After another 4 day incubation period at 21° C and 95% r. h. the disease incidence is assessed.
Compounds of Tables 1 to 9 show good activity in this test
 
-45-
C,-C4haloalkyl, C, C4alkenyl, C7-C, alkynyl, CHO, COOC,C4alkyl, C,-C4alkoxy-C,C4alkyl,
C,-C4haloaikoxy-C,-C4alkyl, cyano or nitro; thienyl, furyl, pyrrolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyi, isothiazotyl, thiadiazolyl, imidazolyl, triazinyl, pyridyl, pyridazinyl, pyrazinyl or pyrimidinyl, which are unsubstituted or substituted by halogen, C,C,haloalkyl, hydroxy, cyano, nitro, CHO,
COOC,C4alkyl, C,-C,haloalkoxy-C,C4alkyl,    C,-C,alkoxy or
C,C,haloalkoxy;
124 is hydrogen, cyano, nitro, halogen, C,C,alkoxy, C,C„halcalkyl,
C7-C4haloalkoxy-C,C4alkyl or C,-C4haloalkoxy;
R,, R,, R7, R, and R9 are identical or different and are each independently of the others hydrogen, halogen, Cl-C,,haloalkyl, C1-C4alkyl, C,C4alkoxy, Cl-Chaloalkoxy, C,C4alkoxy-C,-C4alkyl or CrC7cycloalkyl.
3.    A compound of formula I according to claim 2, wherein X is oxygen.
4.    A compound of formula I according to claim 2, wherein Xis sulfur.
5.    A compound of formula I according to claim 3, wherein R, is hydrogen, C.,-C„alkyl or C.,-C4haloalkyl;
R2 is C,C,,alkyl, C,C3haloalkyl or C,C,alkoxy-C,C,alkyl;
A is Al, A2, A3, A5, A8, A10, A13, A14, A17, A18, A20, A21, A22, A24, A25, A26, A27, A29, A31 or A32;
R3 is C5-C7cydoarkyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, C7-C4alkenyl, C2-CATIcynyl, Ca-CAlkyl or C,C,alltoxy; C5C7cycloalkenyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, CrColkenyl, CZ C4alkynyl, C1-C3alkyl or C,-C,alkoxy; Ca-C7cydOdialkenyl, unsubstituted or mono- to disubstituted by halogen,
hydroxy, C2-C4alkenyi, C2-C4alkynyl, C.,-C,alityl or C,C,alkoxy; thienyl, fury!, isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, which are unsubstituted or substituted by halogen, hydroxy,    C1-C4alkoxy or
C,C4haloalkoxy;
 
-46-
N
(A16)
NAN.s (A21)    (Alt)
(622)    NvS
(A18)
(A23)    N
(819)
(A24)    196,
NON
(A20)
(A25)

Rs,    N-N    N-N
    (A27)    (A28)    (A29)    (A30)
R4
    R7    R5
Rs    0 n    R6    7 R.
(A31)    (A32)
and
R, is C3-C7cycloarkyl unsubstituted or mono- to trisubstituted by halogen, hydroxy,
C,-C4haloalkyl, CfC4alkenyl, 02-C.alkynyl, C,-C4haloalkoxy or C,-C,alkyl; C4-c7cycloalkenyl unsubstituted or mono- to trisubstituted by halogen, hydroxy, C,C4alkoxy,
C2-C,alkenyl, C2-C.,aikynyl, C1-C4haloaikoxy or C1-C4alkyl; Cs-OrcYciodialkertyl unsubstituted or mono- to trisubstituted by halogen, hydroxy, CrOsalkoxy,
CrC„alkenyl, CrChalkynyl, C1-C.baloalkoxy or C,-C.alkyl; thienyl, fury), pyrrolyl, pyrazclyl, oxazolyl, thiazofyl, isoxazolyl, isothiazolyl, thiadiazoiyl, imidazolyl, triazinyl, pyridyl, pyrazinyl, pyridazinyi or pyrimidinyl, which are unsubstituted or substituted by halogen, C1-O3haloalltyl,
hydroxy, cyano, nitro, CHO, C,-C.alkoxy-C,C.,alltyl, COOC,-C.alltyi, C C,haloalkoxy-C,C4alkyl, C1-Colkoxy or C,C5haloalkoxy;
is C1-C7cycloalkyl, C3-C7cycloalkenyl or C5-C7cycloalkadienyl which are unsubstituted or substituted by halogen, C1-Corkoxy,    C,C,haloalltoxy-C,C4atkyl,
C1-Colkyl, C,-C,haloalkyl, C,-04haloalkoxy, C2-C4alkenyl or CrColkynyl; phenyl unsubstituted or substituted by halogen, C1-Colkoxy C1-C6haloalltoxy, C,-C4alkyl,
 
-47-
C,-C,alkynyl, C,C3alkyl or C,-Csalkoxy; Cs-C,cycloalkenyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, C,-C,alkenyl, C,-C4alkynyl, C,-C,alkyl or C,-C3a/koxy; C3-C,cyclodialkenyl, unsubstituted or mono- to disubstituted by halogen, hydroxy, Cs-C4alkenyl, CfC,alkynyl, C,-C3alkyl or C,C3alkoxy; thienyl, furyl isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, which are unsubstituted or substituted by halogen, hydroxy,    C,-C,haloalkyl, C,-C,alkoxy or
C,-C,haloalkoxy;
R3, is C5-C7cycloalkyl, Cs-C7cycloalkenyi or C,C7cycloakadienyl, which are unsubstituted or substituted by halogen, C,-C,alkyl,    C,-C,alkenyi, C2-C,alkynyl, C,-C,haloalkyl or
C.,C,haloalkoxy; phenyl which is unsubstituted or substituted by halogen, C,-C4alkyl, C,-C,alkoxy, C1-C,haloalkyr or C,-C,haloalkoxy; thienyl, fury', isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl which are unsubstituted or substituted by halogen, C,-C4alkyl, C,C4alkoxy, C,-C,haloalicyl or C,-C,haloalkoxy;
R, is hydrogen, halogen, Cu-C,alkyl, C,C,alkoxy, C,-C,haloalityl or Cl-C,haloalkoxy; and R3, Rs, R7 and Fts are identical or different and are each independently of the others hydrogen, C,-C,,alkyl, C,-Csalkoxy, C,-C,haloalkyl or Cr-C,,haloalkoxy.
8. A compound of formula I according to claim 7, wherein
A is Al, AZ A3, All, A20, A21, A24, A25, A26, A27 or A31;
R, is hydrogen or C,-C,AlkYli
R5 is C.,-Csalkyl or C.,-C,alkoxy-C,-Csalkyl;
Rs is cyclohexyl, cyclollexenyl or cyclohexadienyl, which are unsubstituted or mono- to disubstituted by chtoro, bromo,    C,-C.,haloalkyl or C,-C,hajoalkoxy; thienyl, fury',
triazinyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-C4aikyl, Cre,haloallvt or C.,-C4haloalkoxy;
Rs, is cyclohexyl, cyclohexenyl or cycrohexadienyl, which are unsubstituted or substituted by halogen, C1-C4alkyl, C1-C,alltoxy, C1-C4haloalkyl or Cs-C,haloalkoxy; thienyl, furyl, triazinyt, pyridyl, pyrazlnyl, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-C4alkyl, CrC„haloalkyl or C,-C4haroalkoxy;
R, is hydrogen, halogen, C,-Csalkyl, C,-C3hafoalkyr, C,-C3alkoxy or C.,-Cahaloalko)ry; and
Rs, R3, R7 and Rs are identical or different and are each independently of the others hydrogen or C,C3alkyl.
 
-48-
is C,-C,cycroalkyl, C5-C7cycloalkenyl or Ce-C,cycloakadienyl, which are unsubstituted or substituted by halogen, C,-C4alkyl, C,-C4alkoxy, C,-C,alkenyl,    C,C,haloalkyi or
C,-C,haloalkoxy; phenyl which is unsubstituted or substituted by halogen, C,-C,alkyl, C,C,alkoxy, C,-C4haloalkyl or C,-C,haioaticoxy; thienyl, furyl, isoxazolyl, oxazolyl, thiadiazoiyi, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl which are unsubstituted or substituted by halogen, C,-C,alkyl, C,C,alkoxy, C,-C,haloalkyl or C,-C„haloalkoxy;
R, is hydrogen, halogen, C,-C,alkyl, C,-C,alkoxy, C,-C,haloakyl or C,-C,haloalkoxy; and R,,    R, and Ro are identical or different and are each independently of the others
hydrogen, C,-C,alkyl,    or C,-C,haloalkoxy.
6.    A compound of formula I according to claim 5, wherein
A is Al, A2, A3, A17, A20, A21, A24, A25, A26, A27 or A.31;
R, is hydrogen or C,-C.alkyl;
R, is C,C,alkyl or C,-C,alkoxy-C,C,alkyl;
Rats cyclohexyl, cyciohexenyl or cyciohexarlienyl, which are unsubstituted or mono- to disubstituted by chloro, bromo,    CI-C,haloalkyl or C,-C2haloalkoxy; thienyl, furyl,
triazinyl, pyridyl, pyrazinyl, pyrioazinyi or pyrimidirtyl which are unsubstituted or substituted by halogen, C,C,alkyl, CI-C,haloalkyl or C,C,haloalkoxy;
R,„ is cyclohexyl, cydohexenyl or cyclohexadienyl, which are unsubstituted or substituted by halogen, C,-C„alkyl, C C,alkoxy, Cre,haloalkyl or C,-C„haloalkoxy-, thienyl, furyl, hiazinyr, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyi which are unsubstituted or substituted by halogen, C„-Colkyl, C,-C,haloalkyt or C,-C,haloafkOxy;
R, is hydrogen, halogen, C,-C,alicyl,    C,-C,alkoxy or C,-C,haloalkoxy; and
R5, Re, R, and Rn are identical or different and are each independently of the others hydrogen or CrCaalkyl.
7.    A compound of formula 1 according to claim 4, wherein R, is hydrogen, C,-C,alkyl or C,C4haloalicY1i
R2 is C,-C.,allcyl, C,-C,haloalkyl or C,-Csalkoxy-C,-C,alkyl;
A is Al, A2, A3, A5, Ati, A10, A.13, AU, All, A18, A20, A21, A22, A24, A25, A26, A27, A29, A31 or A32;
it is C,-C,cycloalkyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy,
 
-49-
9. A process for the preparation of compounds of formula I which comprises reacting the starting materials according to the scheme
 
FC
001-1
,) SOCl2 or (CIC0)2
in CH2C12 or others,
or without solvent
2) base/ HMA/solvent(THF, toluene, C1-12C12 or others)
 
Base = NEt3 , Hanig-base, Na2CO3 , K2CO3 and others
wherein R,, R2 andA are as defined for formula I in claim 1.
10. A composition for controlling microorganisms and preventing attack and infestation of plants therewith, wherein the active ingredient is a compound as claimed in claim 1 together with a suitable carder.
It Use of a compound of formula 1 according to claim 1 for protecting plants against infestation by phytopathogenic microorganisms.
12. A method of controlling or preventing infestation of cultivated plants by phytopathogenic microorganisms by application of a compound of formula I as claimed in claim 1 to plants, to parts thereof or the locus thereof.
 
What is claimed is
1. A trifluoromethylpyrrolcarboxamide of the formula I
X
 

 
wherein
X is oxygen or sulfur;
R, is hydrogen, CI-C4alkyl unsubstituted or substituted, or halogen;
R3 is C,-C4alkyl unsubstituted or substituted; and
A is orthosubstituted aryl; orthosubstituted heteroaryl; bicycloaryl unsubstituted or substituted; or bicycloheteroaryl unsubstituted or substituted; with the proviso that when X=0
 

 
C3-C7cycloalkyl or unsubstituted C4-C7cycloalkenyl.
2. A compound of formula I according to claim 1, wherein
R., is hydrogen, C,-C„alkyl, C,C4haloalkyl,    C,-C4alkoxy,
C, C,haioalkoxy, C,C4haloalkoxy-C1-C4alkyl or halogen ;
R3 is C1-C4allcyl, 0,-C4haloalkyl, C1-C4alkoxy-C,C4alkyl or 0,-C4haloalkoxy-C,-C4alkyi ; A is a group
 
R3I
\ /    .    _14 R4    R3, '    N—N    R3,    N—N
Rai
(A28)    (A27) R3,    (A28)    (A29)    (A30)

 
and
R3 is C3-C7cycloaikyl unsubstituted or mono- to trisubstituted by halogen, hydroxy, C1-C4alkoxy, C,-C4haloalkyl, C,-C,alkenyl, C,-C,alkynyl, C1-C4haloalkoxy or C,-C,alkyl; C4-C7cycloalkenyl unsubstituted or mono- to trisubstituted by halogen, hydroxy, C,-C,alkoxy, C3-C4haloalkyl, C,-C,alkenyl, C2 C4aikynyl, C1-C4ha(oalkoxy or C,-C,alkyl; C3-C,cycJodiarkenyl unsubstituted or mono- to trisubstituted by halogen, hydroxy, C,-C,alkoxy, C„-C„haloalkyl, C2-C,alkenyi, C2-C4alkynyl, C,-C4haloalkoxy or C1-C4a)kyl; thienyl, furyi, pyrrolyl, pyrazolyi, oxazolyl, thiazotyl, isoxazolyl, isothiazolyl, thiadiazolyl, imidazolyl, triazinyl, benzothienyl, tetrazolyl, 5.6-dihYdro-1,4,2-dioxazinyl, pyridyl, pyrazinyl, pyridazinyl or pydrniclinyl, which are unsubstituted or substituted by halogen, C,-Cehaloalkyl,    hydroxy, cyano, nitro,
cHO, C,-C4alkoxy-C1-C4alkyl. COOC,-C4alltyl, C„-Cpaloalkoxy-C,-C,alkyl, C.,-Colkoxy or
 
Cl-C.haloalkoxy;
R., is C.-C,cycloalkyl, C.-C,cycloalkenyl or C,Cycycloalkadienyl which are unsubstituted or substituted by halogen, C,-Colkoxy, C,-C,alkoxy-C,-C,aikyl. C,-C.haloalkoxy-C,-C,aikyl, C, C4alkyl, C,-C,haloalkyl, C,-C4haloalkoxy, Cre.alkenyi or C,C5alkynyi; phenyl unsubstituted or substituted by halogen, C,-Colkoxy, C,-C,haloalkoxy, C, C4alkyl, C,-C4haloalkyl, C,-C,alkenyi, C2-C, alkynyl, CHO, COOC,-C.alkyl, C,-C4alkoxy-C,C4alkyl, Ci-C4alkyl-C,-C4alkoxy, C1-C4haloalkoxy-C1-C4alkyl, C1-C4haloalkyl-C,C4alkoxy, cyano or
nitro; thienyl, furyi, pyrrolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, imidazolyi, triazinyl, pyridyl, pyridazinyl, pyrazinyl or pyrimidinyl, which are unsubstituted or substituted by halogen, C,-C.haloalkyl,    hydroxy, cyano, nitro, CHO,
COOCI-Colkyl, C,C„haloalkoxy-C1-C4alkyl, Cl-C4alkoxy-C,C4alkyl, C1-Colkoxy or
is hydrogen; cyano; nitro; halogen; C,-C„alkoxy; C,-C4haloalkyr; C,C4alkyl; C,-C4alkoxy-C,-C4alkyl; C6-C7cycloalkyl unsubstituted or substituted by C,-C3alkyl or C,C.haloalkyl; C,C4haloalkoxy-C,C4alkyl; or C,-C4haloalkoxy; and
R., R., R,, R. and R. are identical or different and are each independently of the others hydrogen, halogen, C,-C4haloalkyl, C,-C4alkyl, C,-C„,haloalkoxy-C,-C4alkyl, Cl-C4alkoxy, C1-C,haloalkoxy, C1-Colkoxy-C1-Colkyl or C3-C,cycloalkyl.
3, A compound of formula I according to claim 2, wherein X is oxygen.
4.    A compound of formula I according to claim 2, wherein X is sulfur.
5.    A compound of formula I according to claim 3, wherein R, is hydrogen, Cl-C4afkyl or C1-C4haloarkyl;
R2 is C,-C4allryl, C„-C,haloalkyl or C1-C,aikoxy-C1-C4allcyl;
A is Al, A2, A3, A5, A8, A10, A13, A14, A17, A18, A20, A21, A22, A24, A25, A26, A27, A29, A31 or A32;
R. is C.-C,cycloaikyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, O2-Colkenyl, C5-Cialkynyl, C,C.alkyl or C,C3alkoxy; C.-C7cycloalkenyi, unsubstituted or mono- to trisubstituted by halogen, hydroxy, C2-C4alkenyl, C2-C4alkynyl, Cl-C3alkyl or
 
C,-C,alkoxy; Ce-C7cyclodialkenyl, unsubstituted or mono- to disubstituted by halogen, hydroxy, C2-C,alkenyl, C2-C,alkynyf, C,-C,alkyl or C,-C,alkoxy; thienyl, fury!, isoxazolyl, oxazofyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyf, which are unsubstituted or substituted by halogen, hydroxy, C,-C,alkyl, C1-C4haloarkyl, C,-C‘alkoxy or C,-C,haloalkoxy;
R,, is C5-C7cycloalkyl, C5-C7cycloalkenyl or C5-C7cycloakadienyl, which are unsubstituted or substituted by halogen, C,-C,alkyl, C1-Colkoxy, CrColkenyl, CrC,alkynyl, C,-C,haloalkyl or C,-C,haloalkoxy; phenyl which is unsubstituted or substituted by halogen, C,-C4alkyl, C,-C,alkoxy, CI-C,haroalkyl or C1-C4haloalkoxy; thienyl, furyl, isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyf which are unsubstituted or substituted by halogen, Cl-C4alkyl, C,C4alkoxy, C,-C,haloalkyl or C,-Cihaloalkoxy;
R., is hydrogen; halogen; C,-C,alkyl; C,-C,alkoxy; C5-Cycycloalkyl unsubstituted or substituted by C1-C4alkyl or C,-C,haloalkyl; C,C,haloalkyl; or C,-C,haloalkoxy; and
R5, Re, R7 and R8 are identical or different and are each independently of the others hydrogen, C,-C,alkyl, C,-C,alkoxy, C,-C,haloalkyl or C,-C,haloalkoxy,
6. A compound of formula I according to claim 5, wherein
A is Al, A2, A3, A17, A20, A21, A24, A25, A26, A27 or A31;
R, is hydrogen or C1-C,alkyf;
R2 is C,-C,alkyl or C1-C3alkoxy-C1-C4alkyl;
R, is cyclohexyl, cyclohexenyi or cyclohexadienyl, which are unsubstituted or mono- to disubstituted by chloro, bromo,    C1-C2haloalkyl or C,C2haloalkoxy; thienyl, fury!,
triazinyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-C„alkyl, C,-C,haloalkyl or C,-C,haloalkoxy;
is cyclohexyl, cyclohexenyl or cyclohexadienyl, which are unsubstituted or substituted by halogen, C,-C,alkyl, C,-C,alkoxy, C,-C4haloalkyl or C,-C,haloalkoxy; thienyl, furyl, triazinyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-C,alkyl, C1-C4haloalkyl or C1-C4haloalkoxy;
R4 is hydrogen; halogen; C,-C,alkyl; C1-C4haloalkyl; C5-C7cycloalkyi unsubstituted or substituted by C,-C,aikyl or C1-C4haloalkyl; C,-C,alkoxy; or C1-C4haloalkoxy; and
R5, R6, R7 and R, are identical or different and are each independently of the others hydrogen or C,-C,alkyl,
 
7.    A compound of formula I according to claim 4, wherein
R, is hydrogen, Cl-C,alkyl or CI-Cdhaloalkyl;
R2 is C,-C,alkyl, C,-C,haloalkyl or C1-C3alkoxy-C,-Colkyl;
A is Al, A2, A3, A5, A8, A10, A13, A14, A17, A18, A20, A21, A22, A24, A25, A26, A27, A29, A31 or A32;
R, is C„-C,cycloalkyl, unsubstituted or mono- to trisubstituted by halogen, hydroxy, C2-C,aikenyl, C5-C4alkynyl, C,-Csalkyl or Cl-C,alkoxy; CrC,cycloalkenyi, unsubstituted or mono- to trisubstituted by halogen, hydroxy, CrC,alkenyl, C2-C4alkynyi, C1-C,alkyl or C,-C,alkoxy; C„-C,cycIodialkenyl, unsubstituted or mono- to disubstituted by halogen, hydroxy, CrC„alkenyl, C2-C4alkynyl, C,-C,alkyl or C,-C,alkoxy; thienyl, furyl, isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyi, which are unsubstituted or substituted by halogen, hydroxy, C,-C,alkyl, C,-C,haloalkyl, C,-C,alkoxy or C,-C,haloalkoxy;
R27 is C5-C,cycloalkyl, CrC,cydoalkenyl or CrC,cycloakadienyl, which are unsubstituted or substituted by halogen, C,-C,alkyl, C1-Colkoxy, C,-C,alkenyl, CrC,alkynyl, C,-C,,haloalkyl or C1-C4haloalkoxy; phenyl which is unsubstituted or substituted by halogen, C1-C4alkyl,
C,-C„alkoxy, C,-C4haloalkyl or C1-C4haloalkoxy; thienyl, furyl, isoxazolyl, oxazolyl, thiadiazolyl, triazinyl, pyridyi, pyrimidinyl, pyrazinyl or pyridazinyl which are unsubstituted or substituted by halogen, C1-C4alkyl, C,-C,alkoxy, C,-C,haloalkyl or C1-C4haloalkoxy;
R, is hydrogen; halogen; C,-C,alkyl; C,-C,alkoxy; CrC,cydoalkyl unsubstituted or substituted by C,-Csalkyl or C,-C,haloalkyl; C,-C,haloalkyi; or Cl-C,haloalkoxy; and
R„, R, and R„ are identical or different and are each independently of the others hydrogen, C,C,alkyl, C,C,alkoxy, C,-C,haloalkyl or C,-C,haloalkoxy.
8.    A compound of formula I according to claim 7, wherein
A is Al, A2, A3, A17, A20, A21, A24, P25, A26, A27 or A31;
R, is hydrogen or C,-C,alkyl;
R2 is C,-C,alkyl or Cl-C,alkoxy-C.,-C,alkyl;
R3 is cyclohexyl, cyclohexenyl or cyclohexadienyl, which are unsubstituted or mono- to disubstituted by chloro, bromo, C,-C2alkyl, C,-C,haloalkyl or C,-C,haloalkoxy; thienyl, furyl, triazinyl, pyddyl, pyrazinyi, pyridazinyl or pyrimidinyl which are unsubstituted or substituted by halogen, C,-C,alkyl, C,-C,haloalkyl or CI-C,haloalkoxy;
 
R„ is cyclohexyl, cyclohexenyl or cyclohexadienyl, which are unsubstituted or substituted by halogen, C,-C,alkyl, C,-C,aikoxy, C1-C4haloalkyl or C1-04haloalkoxy; thienyl, furyl, triazinyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidinyi which are unsubstituted or substituted by halogen, C,-C,alkyl, C,-C,haloalkyl or C,-C,haloalkoxy;
R, is hydrogen; halogen; C,-C3alkyl; C,-C,haloalkyl; C5-C,cycloalkyl unsubstituted or substituted by C,-C3alkyl or C,-C3hafoalkyl; C,-C3aIkoxy; or C,-C3haloalkoxy; and
R5, Re, R, and R, are identical or different and are each independently of the others hydrogen or C,-C3alkyl.
9.    A compound of formula I according to claim 3, wherein
A is A1 and
R3 is C5-C,cycloalkyl unsubstituted or monosubstituted by C1-C4alkyl or C,-C,haloalkyl.
10.    A compound of formula I according to claim 9 selected from the group comprising 1-methyl-4-trifluoromethyl-1H-pyrrole-3-carboxylic acid [1'-(3'-methylcyclohexyl)-2- benzamide]; 1-methyl-4-tritluoromethyl-1H-pyrrole-3-carboxylic acid [t'-(3'-ethylcyclohexyl)-2-benzamide]; 1-methyl-4-trifluoromethy1-11-1-pyrrole-3-carboxylic acid [1.-(3'-trifluoromethylcyclohexyl)-2-. benzamide]; 1-methyl-4-trifluoromethyl-11-1-pyrrole-3-carboxylic acid (1 '-(3'-methylcyclopentyl )-2- benzamide]; 1-methyl-4-trifluommethy1-11-1-pyrrole-3-carboxylic acid [1'-(3.-ethylcydopenty1)-2-
benzamide];
1-methyl-4-trifluoromethy1-1H-pyrrole-3-carboxylic acid r-(3'-trifluoromethylcyclopenty0-2- benzamide).
11.    A process for the preparation of compounds of formula I which comprises reacting the starting materials according to the scheme

 

 

 

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