WO2019115338A1

WO2019115338A1 - Process for the preparation of (5-cyano-imidazol-1-yl)ethanone derivatives and intermediates useful therefor

Info

Publication number: WO2019115338A1
Application number: PCT/EP2018/083768
Authority: WO
Inventors: Christoph SÄMANN; Sergii Pazenok
Original assignee: Bayer Aktiengesellschaft
Priority date: 2017-12-12
Filing date: 2018-12-06
Publication date: 2019-06-20
Also published as: TW201936583A

Abstract

The present invention relates to a process for preparing 1-(5-cyano-imidazol-1-yl)ethan-2-one derivatives of formula (I) by reacting in a first step an imidazole of formula (II) with a ketone of formula (III), wherein R1, R2 and R3 are defined as disclosed in the specification, and cleaving in a second step the carbamoyl group from the resulting compound, as well as to specific intermediates useful in this process.

Description

Process for the preparation of (5-cvano-imidazol-l-yl )ethanone derivatives and intermediates useful therefor

The present invention relates to a process for preparing (5-cyano-imidazol-l-yl) ethanone derivatives and to specific intermediates that are particularly useful in this process.

Certain 5-substituted imidazolylmethyl derivatives are known to be useful in the field of crop protection, in particular as fungicides. WO 2016/156290 Al discloses such 5-substituted imidazolylmethyl derivatives and several routes to synthesize those. One of said routes is referred to in WO 2016/156290 Al as process M and comprises reacting suitable (5-substituted imidazol-l-yl)ethanone derivatives and Grignard reagents. The respective (5-substituted imidazol- 1 -yl)ethanone derivatives can be obtained according to the procedures referred to in WO 2016/156290 Al as processes J and K. Said processes provide access to (5- cyano-imidazol-l-yl)ethanone derivatives. However, they have certain disadvantages. In process J 5- cyano-l //-imidazole is reacted with a suitable ketone in order to alkylate the imidazole nitrogen atom in 1- position. Unfortunately, such reaction is not sufficiently regioselective to result only in the desired alkylation. There is also considerable alkylation of the imidazole nitrogen atom in 3-position. This not only reduces the yield of the desired compounds but also necessitates laborious separation of the resulting regioisomers. Process K addresses this problem by introducing a protecting group at the imidazole nitrogen atom that is not supposed to be alkylated. However, such procedure involves two additional process steps, namely protection and deprotection of the nitrogen atom. Moreover, in many cases deprotecting the nitrogen atom requires use of transition metal compounds. Such use is unfavorable from an economical point of view. Moreover, since the transition metal compound may interfere with any subsequent reaction of the (5-substituted imidazol- 1 -yl)ethanone derivative, it must be thoroughly separated. Therefore, to allow efficient synthesis in an industrial scale further improvement of the known processes is desirable.

Hence, object of the invention is providing an improved process for the synthesis of (5-cyano-imidazol-l- yljethanone derivatives as well as novel compounds that are particularly useful intermediates in such process.

Surprisingly, it has been found that (5-cyano-imidazol-l-yl)ethanone derivatives can be synthesized in high yield without introducing any protecting group at one of the imidazole nitrogen atoms by reacting a readily available 4-carbamoyl-5-cyanoimidazole with a suitable ketone and subsequent cleavage of the carbamoyl group from the resulting product.

Accordingly, subject of this invention is a process for preparing compounds of formula (I)

wherein

R¹ represents hydrogen, Ci-Cs-alkyl, Ci-Cs-haloalkyl, C₂-Cs-alkenyl, C₂-Cs-haloalkenyl, C₂-Cs-alkynyl, C₂-C₈-haloalkynyl, phenyl-C₂-Cs-alkynyl, [tri(Ci-Cs-alkyl)silyl]phenyl-C₂-C₈-alkynyl, C₃-C₇- cycloalkyl, bicycloalkyl, C₃-C₇-cycloalkyl-Ci-C₄-alkyl, C₃-C₇-cycloalkyl-C₃-C₇-cycloalkyl, C₃-C₇- cycloalkenyl, tri(Ci-C₈-alkyl)silyl-Ci-C₄-alkyl, tri(Ci-C₈-alkyl)silyl-C₃-C₇-cycloalkyl, or C₆-Ci₄-aryl, wherein the phenyl-C₂-C₈-alkynyl, [tri(Ci-C₈-alkyl)silyl]phenyl-C₂-C₈-alkynyl, C₃-C₇-cycloalkyl, bicycloalkyl, C₃-C₇-cycloalkyl-Ci-C₄-alkyl, C₃-C₇-cycloalkyl-C₃-C₇-cycloalkyl, C₃-C₇-cycloalkenyl, tri(Ci-C₈-alkyl)silyl-Ci-C₄-alkyl, tri(Ci-C₈-alkyl)silyl-C₃-C₇-cycloalkyl, and C₆-Ci₄-aryl is non- substituted or substituted by one or more group(s) selected from halogen, cyano, Ci-C₄-alkyl, C₁-C₄- haloalkyl, Ci-C₄-alkoxy, Ci-C₄-haloalkoxy, Ci-C₄-alkylthio and Ci-C₄-haloalkylthio; and

R² represents hydrogen, Ci-Cs-alkyl, or Ce-Cw-aryl; by reacting in a first step A) an imidazole of formula (II)

(n),

wherein

R² is defined as in formula (I); with a ketone of formula (III),

^R3\A_RI (PI),

wherein R³ represents chlorine, bromine, iodine, Ci-Cs-alkylsulfonate, or C₆-Ci₄-arylsulfonate, wherein the G,- Ci₄-arylsulfonate is non-substituted or substituted by one or more group(s) selected from halogen, Ci-C₄-alkyl, and Ci-C₄-haloalkyl; and

R¹ is defined as in formula (I), to yield a compound of formula (IV),

wherein

R¹ and R² are defined as in formula (I), and cleaving in a further step B) the carbamoyl group from the compound of formula (IV). Cleaving of the carbamoyl group from the compound of formula (IV) as used throughout this specification results in the respective compound of formula (I), i.e. the carbamoyl group is replaced by hydrogen.

Formula (I) provides a general definition of the (5-cyano-imidazol-l-yl)ethanone derivatives obtainable by the process according to the invention. Preferred definitions of the symbols used in the formulae shown above and below are given below. These definitions apply to the compounds of formula (I) and likewise to all educts and intermediates, e.g. the imidazoles of formula (II), the ketones of formula (III) and the intermediates of formulae (IV) and (V).

R¹ preferably represents Ci-Cs-alkyl, Ci-Cs-haloalkyl, C₂-C₇-alkenyl, C₂-C₇-haloalkenyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, C₁-C₄- alkylthio- or Ci-C₄-haloalkylthio-substituted C₃-C₇-cycloalkyl or optionally halogen-, cyano-, C₁-C₄- alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio- substituted C₆-Ci₄-aryl.

R¹ more preferably represents Ci-Cs-alkyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₃-C₇- cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, C₁-C₄- haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted Ce-Cw-aryl. R¹ more preferably represents Ci-C₄-alkyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-haloalkoxy-, Ci-C₄-alkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₃-C₆- cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, C₁-C₄- haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted phenyl.

R¹ more preferably represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, /c/7-butyl, cyclopropyl, 1 -halocyclopropyl, l-(Ci-C₄-alkyl)cyclopropyl, or optionally halogen-substituted phenyl.

R¹ most preferably represents isopropyl, ieri-butyl, cyclopropyl, l-chlorocyclopropyl, 1- fluorocyclopropyl, 1 -methylcyclopropyl, phenyl or 2,4-difluorophenyl.

R² preferably represents H, Ci-C₄-alkyl, or phenyl.

R² more preferably represents H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, teri-butyl, or phenyl.

R² more preferably represents H, methyl, or phenyl.

R² most preferably represents H.

R³ preferably represents chlorine, bromine, iodine, Ci-C₄-alkylsulfonate, or C₆-arylsulfonate, wherein the C₆-arylsulfonate is non-substituted or substituted by one or more group(s) selected from halogen, Ci-C₄-alkyl, and Ci-C₄-haloalkyl.

R³ more preferably represents chlorine, bromine, iodine, methylsulfonate, ethylsulfonate, n- propylsulfonate, isopropylsulfonate, n-butylsulfonate, isobutylsulfonate, ieri-butylsulfonate or phenylsulfonate, wherein the phenylsulfonate is non-substituted or substituted by one or more group(s) selected from fluorine, chlorine, bromine, iodine, methyl, and CF₃.

R³ more preferably represents bromine, iodine, methylsulfonate, or 4-methylbenzenesulfonate.

R³ more preferably represents bromine or chlorine.

R³ most preferably represents bromine.

The symbol definitions and explanations given above in general terms or stated within preferred ranges can be combined with one another as desired, i.e. including between the particular ranges and preferred ranges.

They apply both to the end products and correspondingly to educts and intermediates. In addition, individual definitions may not apply. Preference is given to those cases in which each of the symbols have the abovementioned preferred definitions.

Particular preference is given to those cases in which each of the symbols have the abovementioned more and/or most preferred definitions. Hence, particular preferred is a process for preparing a compound of formula (I), wherein the compound of formula (I) is represented by formula (la)

O

R J

\W N

(la),

wherein

R¹ represents hydrogen, Ci-Cs-alkyl, Ci-Cs-haloalkyl, C₂-Cs-alkenyl, C₂-Cs-haloalkenyl, C₂-Cs-alkynyl, C₂-C₈-haloalkynyl, phenyl-C₂-Cs-alkynyl, [tri(Ci-C₈-alkyl)silyl]phenyl-C₂-Cs-alkynyl, C₃-C₇- cycloalkyl, bicycloalkyl, C₃-C₇-cycloalkyl-Ci-C₄-alkyl, C₃-C₇-cycloalkyl-C₃-C₇-cycloalkyl, C₃-C₇- cycloalkenyl, tri(Ci-Cs-alkyl)silyl-Ci-C₄-alkyl, tri(Ci-Cs-alkyl)silyl-C₃-C₇-cycloalkyl, or C₆-Ci₄-aryl, wherein the phenyl-C₂-C₈-alkynyl, [tri(Ci-C₈-alkyl)silyl]phenyl-C₂-Cs-alkynyl, C₃-C₇-cycloalkyl, bicycloalkyl, C₃-C₇-cycloalkyl-Ci-C₄-alkyl, C₃-C₇-cycloalkyl-C₃-C₇-cycloalkyl, C₃-C₇-cycloalkenyl, tri(Ci-C₈-alkyl)silyl-Ci-C₄-alkyl, tri(Ci-Cs-alkyl)silyl-C₃-C₇-cycloalkyl, and C₆-Ci₄-aryl is non- substituted or substituted by one or more group(s) selected from halogen, cyano, Ci-C₄-alkyl, C₁-C₄- haloalkyl, Ci-C₄-alkoxy, Ci-C₄-haloalkoxy, Ci-C₄-alkylthio and Ci-C₄-haloalkylthio, preferably Ci-Cs-alkyl, Ci-Cs-haloalkyl, C₂-C₇-alkenyl, C₂-C₇-haloalkenyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci- C₄-haloalkylthio-substituted C₃-C₇-cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, C₁-C₄- haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₆-Ci₄-aryl, more preferably Ci-Cs-alkyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, C₁-C₄- alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₃-C₇-cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-

C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₆-Ci₄-aryl, more preferably Ci-C₄-alkyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, C₁-C₄- haloalkoxy-, Ci-C₄-alkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₃-C₆-cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci- C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted phenyl, more preferably represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, /^/7-butyl, cyclopropyl, 1 -halocyclopropyl, l-(Ci-C₄-alkyl)cyclopropyl, or optionally halogen-substituted phenyl and most preferably isopropyl, /c/7-butyl, cyclopropyl, 1 -chlorocyclopropyl, l-fluorocyclopropyl, 1- methylcyclopropyl, phenyl or 2,4-difluorophenyl.

In the definitions of the symbols given in the above and below formulae, collective terms were used which are generally representative of the following substituents:

Halogen: fluorine, chlorine, bromine or iodine. Halogen-substitution is generally indicated by the prefix halo, halogen or halogeno.

Alkyl: saturated, straight-chain or branched hydrocarbyl radical having 1 to 8, preferably 1 to 6, and more preferably 1 to 4 carbon atoms, for example (but not limited to) Ci-C₆-alkyl such as methyl, ethyl, propyl (n-propyl), 1 -methylethyl (iso-propyl), butyl (n-butyl), l-methylpropyl (sec-butyl), 2-methylpropyl (iso butyl), l,l-dimethylethyl (tert-butyl), pentyl, l-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2- dimethylpropyl, l-ethylpropyl, l,l-dimethylpropyl, 1 ,2-dimethylpropyl, hexyl, 1 -methylpentyl, 2- methylpentyl, 3 -methylpentyl, 4-methylpentyl, l,l-dimethylbutyl, l,2-dimethylbutyl, l,3-dimethylbutyl,

2.2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, l,l,2-trimethylpropyl,

1.2.2-trimethylpropyl, 1 -ethyl- 1 -methylpropyl and 1 -ethyl-2-methylpropyl. Particularly, said group is a Ci- C₄-alkyl group, e.g. a methyl, ethyl, propyl, 1 -methylethyl (isopropyl), butyl, 1 -methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl) or l,l-dimethylethyl (tert-butyl) group. This definition also applies to alkyl as part of a composite substituent, for example cycloalkylalkyl, hydroxyalkyl etc., unless defined elsewhere like, for example, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, haloalkyl or haloalkylsulfanyl.

Alkenyl: unsaturated, straight-chain or branched hydrocarbyl radicals having 2 to 8, preferably 2 to 6, and more preferably 2 to 4 carbon atoms and one double bond in any position, for example (but not limited to) C₂-C₆-alkenyl such as vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, isopropenyl, homoallyl, (E)-but- 2-enyl, (Z)-but-2-enyl, (E)-but-l-enyl, (Z)-but-l-enyl, 2-methylprop-2-enyl, l-methylprop-2-enyl, 2- methylprop- 1 -enyl, (E)-l-methylprop-l-enyl, (Z)- 1 -methylprop- 1 -enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)- pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-l-enyl, (Z)-pent-l-enyl, 3- methylbut-3-enyl, 2- methylbut-3-enyl, l-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2- enyl, (E)- 1 -methylbut-2-enyl, (Z)-l- methylbut-2-enyl, (E)-3-methylbut-l-enyl, (Z)-3-methylbut-l-enyl, (E)-2- methylbut-l-enyl, (Z)-2-methylbut-l-enyl, (E)- 1 -methylbut- 1 -enyl, (Z)-l- methylbut-l-enyl, 1,1- dimethylprop-2-enyl, 1-ethylprop-l-enyl, 1 -propylvinyl, 1- isopropylvinyl, (E)-3,3-dimethylprop-l-enyl, (Z)-3,3-dimethylprop-l-enyl, hex-5-enyl, (E)-hex-4- enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-l-enyl, (Z)-hex-l-enyl, 4-methylpent-4-enyl, 3-methylpent-4-enyl, 2-methylpent-4-enyl, 1- methylpent-4-enyl, 4-methylpent-3-enyl, (E)-3-methylpent-3-enyl, (Z)-3- methylpent-3-enyl, (E)-2-methylpent-3-enyl, (Z)-2-methylpent-3-enyl, (E)-l- methylpent-3-enyl, (Z)-l - methylpent-3-enyl, (E)-4-methylpent-2-enyl, (Z)-4- methylpent-2-enyl, (E)-3-methylpent-2-enyl, (Z)-3- methylpent-2-enyl, (E)-2- methylpent-2-enyl, (Z)-2-methylpent-2-enyl, (E)-l -methylpent-2-enyl, (Z)-l- methylpent-2-enyl, (E)-4-methylpent- 1 -enyl, (Z)-4-methylpent-l-enyl, (E)-3- methylpent-l-enyl, (Z)-3- methylpent-l -enyl, (E)-2-methylpent- 1 -enyl, (Z)-2- methylpent-l-enyl, (E)-l -methylpent-l-enyl, (Z)-l- methylpent- 1 -enyl, 3-ethylbut- 3-enyl, 2-ethylbut-3-enyl, l-ethylbut-3-enyl, (E)-3-ethylbut-2-enyl, (Z)-3- ethylbut-2-enyl, (E)-2-ethylbut-2-enyl, (Z)-2-ethylbut-2-enyl, (E)- 1 -ethylbut-2-enyl, (Z)-l-ethylbut-2-enyl, (E)-3-ethylbut-l-enyl, (Z)-3-ethylbut-l-enyl, 2-ethylbut- 1 -enyl, (E)-l-ethylbut-l-enyl, (Z)-l-ethylbut-l- enyl, 2-propylprop-2-enyl, 1 -propylprop-2- enyl, 2-isopropylprop-2-enyl, 1 -isopropylprop-2-enyl, (E)-2- propylprop-l-enyl, (Z)- 2-propylprop-l-enyl, (E)-l-propylprop-l-enyl, (Z)- 1 -propylprop- 1 -enyl, (E)-2- isopropylprop-l-enyl, (Z)-2-isopropylprop-l-enyl, (E)-l-isopropylprop-l-enyl, (Z)-l- isopropylprop- 1 - enyl, l-(l,l-dimethylethyl)ethenyl, buta-l,3-dienyl, penta-l,4-dienyl, hexa-l,5-dienyl or methylhexadienyl. Particularly, said group is vinyl or allyl. This definition also applies to alkenyl as part of a composite substituent, for example haloalkenyl etc., unless defined elsewhere.

Alkynyl: straight-chain or branched hydrocarbyl groups having 2 to 8, preferably 2 to 6, and more preferably 2 to 4 carbon atoms and one triple bond in any position, for example (but not limited to) C2-C6- alkynyl, such as ethynyl, prop-l-ynyl, prop-2 -ynyl, but-l-ynyl, but-2-ynyl, but-3-ynyl, l-methylprop-2- ynyl, pent- 1 -ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, 2-methylbut-3-ynyl, 1 -methylbut-3-ynyl, 1- methylbut-2-ynyl, 3-methylbut-l-ynyl, l-ethylprop-2-ynyl, hex- 1 -ynyl, hex-2-ynyl, hex-3 -ynyl, hex-4- ynyl, hex-5-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, l-methylpent-4-ynyl, 2-methylpent-3-ynyl, l-methylpent-3-ynyl, 4-methylpent-2-ynyl, l-methylpent-2-ynyl, 4-methylpent- 1 -ynyl, 3-methylpent-l- ynyl, 2-ethylbut-3-ynyl, l-ethylbut-3-ynyl, l-ethylbut-2-ynyl, 1 -propylprop-2-ynyl, 1 -isopropylprop-2- ynyl, 2,2-dimethylbut-3-ynyl, l,l-dimethylbut-3-ynyl, l,l-dimethylbut-2-ynyl, or 3,3-dimethylbut-l-ynyl group. Particularly, said alkynyl group is ethynyl, prop-l-ynyl, or prop-2-ynyl. This definition also applies to alkynyl as part of a composite substituent, for example haloalkynyl etc., unless defined elsewhere.

Alkoxy: saturated, straight-chain or branched alkoxy radicals having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms, for example (but not limited to) Ci-C₆-alkoxy such as methoxy, ethoxy, propoxy, 1 -methylethoxy, butoxy, 1 -methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1- methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, 1 -ethylpropoxy, 1,1- dimethylpropoxy, 1 ,2-dimethylpropoxy, hexoxy, 1 -methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4- methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3- dimethylbutoxy, 3,3-dimethylbutoxy, 1 -ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2- trimethylpropoxy, 1 -ethyl- 1 -methylpropoxy and l-ethyl-2-methylpropoxy. This definition also applies to alkoxy as part of a composite substituent, for example haloalkoxy, alkynylalkoxy, etc., unless defined elsewhere.

Alkoxycarbonyl: an alkoxy group which has 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms (as specified above) and is bonded to the skeleton via a carbonyl group (-C(=0)-). This definition also applies to alkoxycarbonyl as part of a composite substituent, for example cycloalkylalkoxycarbonyl etc., unless defined elsewhere.

Alkylsulfanyl: saturated, straight-chain or branched alkylsulfanyl radicals having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms, for example (but not limited to) Ci-C₆-alkylsulfanyl such as methylsulfanyl, ethylsulfanyl, propylsulfanyl, 1 -methylethylsulfanyl, butylsulfanyl, 1 -methylpropyl- sulfanyl, 2-methylpropylsulfanyl, 1,1-dimethylethylsulfanyl, pentylsulfanyl, 1-methylbutylsulfanyl, 2- methylbutylsulfanyl, 3-methylbutylsulfanyl, 2,2-dimethylpropylsulfanyl, 1 -ethylpropylsulfanyl, 1,1- dimethylpropylsulfanyl, 1,2-dimethylpropylsulfanyl, hexylsulfanyl, 1 -methylpentylsulfanyl, 2- methylpentylsulfanyl, 3 -methylpentylsulfanyl, 4-methylpentylsulfanyl, 1,1-dimethylbutylsulfanyl, 1,2- dimethylbutylsulfanyl, 1 ,3-dimethylbutylsulfanyl, 2,2-dimethylbutylsulfanyl, 2,3-dimethylbutylsulfanyl, 3,3-dimethylbutylsulfanyl, 1 -ethylbutylsulfanyl, 2-ethylbutylsulfanyl, 1,1,2-trimethylpropylsulfanyl, 1,2,2- trimethylpropylsulfanyl, 1 -ethyl- 1-methylpropylsulfanyl and 1 -ethyl-2-methylpropylsulfanyl. This definition also applies to alkylsulfanyl as part of a composite substituent, for example haloalkylsulfanyl etc., unless defined elsewhere.

Alkylsulfinyl: saturated, straight-chain or branched alkylsulfinyl radicals having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms, for example (but not limited to) Ci-C₆-alkylsulfinyl such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl, butylsulfinyl, 1 -methylpropylsulfinyl, 2-methylpropylsulfinyl, 1,1-dimethylethylsulfinyl, pentylsulfinyl, 1 -methylbutylsulfinyl, 2- methylbutylsulfinyl, 3 -methylbutylsulfinyl, 2,2-dimethylpropylsulfinyl, 1 -ethylpropylsulfinyl, 1,1- dimethylpropylsulfinyl, 1,2-dimethylpropylsulfinyl, hexylsulfinyl, 1-methylpentylsulfinyl, 2-methylpentyl- sulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethyl- butylsulfinyl, 1,3-dimethylbutylsulfinyl, 2,2-dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3- dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1,2,2- trimethylpropylsulfinyl, 1 -ethyl- 1 -methylpropylsulfinyl and l-ethyl-2-methylpropylsulfinyl. This definition also applies to alkylsulfinyl as part of a composite substituent, for example haloalkylsulfinyl etc., unless defined elsewhere.

Alkylsulfonyl: saturated, straight-chain or branched alkylsulfonyl radicals having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms, for example (but not limited to) Ci-C₆-alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1 -methylethylsulfonyl, butylsulfonyl, 1 -methylpropyl- sulfonyl, 2-methylpropylsulfonyl, 1,1-dimethylethylsulfonyl, pentylsulfonyl, 1 -methylbutylsulfonyl, 2- methylbutylsulfonyl, 3 -methylbutylsulfonyl, 2,2-dimethylpropylsulfonyl, 1 -ethylpropylsulfonyl, 1,1- dimethylpropylsulfonyl, 1 ,2-dimethylpropylsulfonyl, hexylsulfonyl, l-methylpentylsulfonyl, 2-methyl- pentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, l,l-dimethylbutylsulfonyl, 1,2- dimethylbutylsulfonyl, 1 ,3-dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3 -dimethylbutylsulfonyl, 1 -ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1 , 1 ,2-trimethylpropylsulfbnyl, 1 ,2,2-trimcthylpmpylsulfonyl, 1 -ethyl- l-methylpropylsulfonyl and 1 -ethyl-2 -methylpropylsulfonyl. This definition also applies to alkylsulfonyl as part of a composite substituent, for example alkylsulfonylalkyl etc., unless defined elsewhere.

Monoalkylamino represents an amino radical having one alkyl residue with 1 to 4 carbon atoms attached to the nitrogen atom. Non-limiting examples include methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino and tert-butylamino.

Dialkylamino represents an amino radical having two independently selected alkyl residues with 1 to 4 carbon atoms each attached to the nitrogen atom. Non-limiting examples include /V,/V-di methylamino, /V,/V-dicthylamino, /V,/V-di isopropylamino, /V-cthyl-/V-mcthylamino, /V-mcthyl-/V-n-pmpylamino, /V-iso- propyl-N-n-propylamino and /V-tcrt-butyl-/V-mcthylamino.

Cycloalkyl: monocyclic, saturated hydrocarbyl groups having 3 to 10, preferably 3 to 8 and more preferably 3 to 6 carbon ring members, for example (but not limited to) cyclopropyl, cyclopentyl and cyclohexyl. This definition also applies to cycloalkyl as part of a composite substituent, for example cycloalkylalkyl etc., unless defined elsewhere.

Cycloalkenyl: monocyclic, partially unsaturated hydrocarbyl groups having 3 to 10, preferably 3 to 8 and more preferably 3 to 6 carbon ring members, for example (but not limited to) cyclopropenyl, cyclopentenyl and cyclohexenyl. This definition also applies to cycloalkenyl as part of a composite substituent, for example cycloalkenylalkyl etc., unless defined elsewhere.

Cycloalkoxy: monocyclic, saturated cycloalkyloxy radicals having 3 to 10, preferably 3 to 8 and more preferably 3 to 6 carbon ring members, for example (but not limited to) cyclopropyloxy, cyclopentyloxy and cyclohexyloxy. This definition also applies to cycloalkoxy as part of a composite substituent, for example cycloalkoxyalkyl etc., unless defined elsewhere.

Haloalkyl: straight-chain or branched alkyl groups having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms (as specified above), where some or all of the hydrogen atoms in these groups are replaced by halogen atoms as specified above, for example (but not limited to) Ci-C3-haloalkyl such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1 -chloroethyl, 1- bromoethyl, 1 -fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2- chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and 1,1,1- trifluoroprop-2-yl. This definition also applies to haloalkyl as part of a composite substituent, for example haloalkylaminoalkyl etc., unless defined elsewhere.

Haloalkenyl and haloalkynyl are defined analogously to haloalkyl except that, instead of alkyl groups, alkenyl and alkynyl groups are present as part of the substituent.

Haloalkoxy: straight-chain or branched alkoxy groups having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms (as specified above), where some or all of the hydrogen atoms in these groups are replaced by halogen atoms as specified above, for example (but not limited to) Ci-C₃-haloalkoxy such as chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloro fluoromethoxy, dichloro fluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2- fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy and l,l,l-trifluoroprop-2-oxy. This definition also applies to haloalkoxy as part of a composite substituent, for example haloalkoxyalkyl etc., unless defined elsewhere.

Haloalkylsulfanyl: straight-chain or branched alkylsulfanyl groups having 1 to 8, preferably 1 to 6 and more preferably 1 to 4 carbon atoms (as specified above), where some or all of the hydrogen atoms in these groups are replaced by halogen atoms as specified above, for example (but not limited to) C₁-C₃- haloalkylsulfanyl such as chloromethylsulfanyl, bromomethylsulfanyl, dichloromethylsulfanyl, trichloromethylsulfanyl, fluoromethylsulfanyl, difluoromethylsulfanyl, trifluoromethylsulfanyl, chlorofluoromethylsulfanyl, dichlorofluoromethylsulfanyl, chlorodifluoromethylsulfanyl, 1 -chloro- ethylsulfanyl, 1 -bromoethylsulfanyl, 1-fluoroethylsulfanyl, 2-fluoroethylsulfanyl, 2,2-difluoroethyl- sulfanyl, 2,2,2-trifluoroethylsulfanyl, 2-chloro-2-fluoroethylsulfanyl, 2-chloro-2,2-difluoroethylsulfanyl, 2,2-dichloro-2-fluoroethylsulfanyl, 2,2,2-trichloroethylsulfanyl, pentafluoroethylsulfanyl and 1,1,1- trifluoroprop-2-ylsulfanyl. This definition also applies to haloalkylsulfanyl as part of a composite substituent, for example haloalkylsulfanylalkyl etc., unless defined elsewhere.

Aryl: mono-, bi- or tricyclic aromatic or partially aromatic group having 6 to 14 carbon atoms, for example (but not limited to) phenyl, naphthyl, tetrahydronapthyl, indenyl and indanyl. The binding to the superordinate general structure can be carried out via any possible ring member of the aryl residue. Aryl is preferably selected from phenyl, 1 -naphthyl and 2-naphthyl. Phenyl is particularly preferred.

Heteroaryl: 5 or 6-membered cyclic aromatic group containing at least 1, if appropriate also 2, 3, 4 or 5 heteroatoms, wherein the heteroatoms are each selected independently of one another from the group S, N and O, and which group can also be part of a bi- or tricyclic system having up to 14 ring members, wherein the ring system can be formed with one or two further cycloalkyl, cycloalkenyl, heterocyclyl, aryl and/or heteroaryl residues and wherein benzofused 5 or 6-membered heteroaryl groups are preferred. The binding to the superordinate general structure can be carried out via any possible ring member of the heteroaryl residue. Examples of 5-membered heteroaryl groups which are attached to the skeleton via one of the carbon ring members are fur-2-yl, fur-3-yl, thien-2-yl, thien-3-yl, pyrrol-2-yl, pyrrol-3-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, imidazol-2-yl, imidazole-4-yl, l,2,4-oxadiazol-3-yl, l,2,4-oxadiazol-5-yl, l,2,4-thiadiazol-3-yl, l,2,4-thiadiazol-5-yl,

1.2.4-triazol-3-yl, l,3,4-oxadiazol-2-yl, l,3,4-thiadiazol-2-yl and l,3,4-triazol-2-yl. Examples of 5- membered heteroaryl groups which are attached to the skeleton via a nitrogen ring member are pyrrol- l-yl, pyrazol-l-yl, l,2,4-triazol-l-yl, imidazol-l-yl, l,2,3-triazol-l-yl and l,3,4-triazol-l-yl. Examples of 6-membered heteroaryl groups are pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyridazin-3- yl, pyridazin-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazine-2-yl, l,3,5-triazin-2-yl, 1,2,4- triazin-3-yl and l,2,4,5-tetrazin-3-yl. Examples of benzofused 5-membered heteroaryl groups are indol-

1-yl, indol-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, indol-7-yl, benzimidazol-l-yl, benzimidazol-

2-yl, benzimidazol-4-yl, benzimidazol-5-yl, indazol-l-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol- 6-yl, indazol-7-yl, indazol-2-yl, 1 -benzofuran-2-yl, l-benzofuran-3-yl, l-benzofuran-4-yl, l-benzofuran-5- yl, l-benzofuran-6-yl, l-benzofuran-7-yl, 1 -benzothiophen-2-yl, l-benzothiophen-3-yl, 1 -benzothiophen- 4-yl, l-benzothiophen-5-yl, 1 -benzothiophen-6-yl, l-benzothiophen-7-yl, l,3-benzothiazol-2-yl, 1,3- benzothiazol-4-yl, l,3-benzothiazol-5-yl, l,3-benzothiazol-6-yl, l,3-benzothiazol-7-yl, l,3-benzoxazol-2- yl, l,3-benzoxazol-4-yl, l,3-benzoxazol-5-yl, l,3-benzoxazol-6-yl and l,3-benzoxazol-7-yl. Examples of benzofused 6-membered heteroaryl groups are quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-5- yl, quinolin-6-yl, quinolin-7-yl, quinolin-8-yl, isoquinolin-l-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl and isoquinolin-8-yl. Further examples of 5- or 6- membered heteroaryls which are part of a bicyclic ring system are l,2,3,4-tetrahydroquinolin-l-yl, 1 ,2,3,4- tetrahydroquinolin-2-yl, l,2,3,4-tetrahydroquinolin-7-yl, 1 ,2,3,4-tetrahydroquinolin-8-yl, 1 ,2,3,4- tetrahydroisoquinolin- 1 -yl, 1 ,2,3,4-tetrahydroisoquinolin-2-yl, l,2,3,4-tetrahydroisoquinolin-5-yl, 1 ,2,3,4- tetrahydroisoquinolin-6-yl and l,2,3,4-tetrahydroisoquinolin-7-yl. This definition also applies to heteroaryl as part of a composite substituent, for example heteroarylalkyl etc., unless defined elsewhere.

Heterocyclyl: three- to seven-membered, saturated or partially unsaturated heterocyclic group containing at least one, if appropriate up to four heteroatoms and/or heterogroups independently selected from the group consisting of N, O, S, S(=0), S(=0)₂ and di-(Ci-C4)alkylsilyl, which group can be benzofused. The binding to the superordinate general structure can be carried out via a ring carbon atom or, if possible, via a ring nitrogen atom of the heterocyclic group. Saturated heterocyclic groups in this sense are for example (but not limited to) oxiranyl, aziridinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, isoxazolidin-3-yl, isoxazolidin-4-yl, isoxazolidin-5- yl, isothiazolidin-3-yl, isothiazolidin-4-yl, isothiazolidin-5-yl, pyrazolidin-3-yl, pyrazolidin-4-yl, pyrazolidin-5-yl, oxazolidin-2-yl, oxazolidin-4-yl, oxazolidin-5-yl, thiazolidin-2-yl, thiazolidin-4-yl, thiazolidin-5-yl, imidazolidin-2-yl, imidazolidin-4-yl, l,2,4-oxadiazolidin-3-yl, l,2,4-oxadiazolidin-5-yl,

1.3.4-oxadiazolidin-2-yl, 1 ,2,4-thiadiazolidin-3 -yl, 1 ,2,4-thiadiazolidin-5-yl, 1 ,3,4-thiadiazolidin-2-yl, l,2,4-triazolidin-3-yl, l,3,4-triazolidin-2-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, l,3-dioxan-5-yl, tetrahydropyran-2-yl, tetrahydropyran-4-yl, tetrahydrothien-2-yl, hexahydropyridazin-3-yl, hexa- hydropyridazin-4-yl, hexahydropyrimidin-2-yl, hexahydropyrimidin-4-yl, hexahydropyrimidin-5-yl, piperazin-2-yl, l,3,5-hexahydrotriazin-2-yl and l,2,4-hexahydrotriazin-3-yl. Partially unsaturated heterocyclic groups in this sense are for example (but not limited to) 2,3-dihydrofur-2-yl, 2,3-dihydrofur-

3-yl, 2,4-dihydrofur-2-yl, 2,4-dihydrofur-3-yl, 2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl, 2,4- dihydrothien-2-yl, 2,4-dihydrothien-3-yl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 2-isoxazolin-3-yl, 3-isoxazolin-3-yl, 4-isoxazolin-3-yl, 2-isoxazolin-4-yl, 3-isoxazolin-4-yl, 4-isoxazolin-

4-yl, 2-isoxazolin-5-yl, 3-isoxazolin-5-yl, 4-isoxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4- isothiazolin-3-yl, 2-isothiazolin-4-yl, 3-isothiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3- isothiazolin-5-yl, 4-isothiazolin-5-yl, 2,3-dihydropyrazol-l-yl, 2,3-dihydropyrazol-2-yl, 2,3- dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropyrazol-5-yl, 3,4-dihydropyrazol-l-yl, 3,4- dihydropyrazol-3-yl, 3,4-dihydropyrazol-4-yl, 3,4-dihydropyrazol-5-yl, 4,5-dihydropyrazol-l-yl, 4,5- dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3- dihydrooxazol-3-yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4- dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl, 3,4-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4- dihydrooxazol-3-yl, 3,4-dihydrooxazol-4-yl. Examples of benzofused heterocyclic groups are indolin-l- yl, indolin-2-yl, indolin-3-yl, isoindolin-l-yl, isoindolin-2-yl, 2,3-dihydrobenzofuran-2-yl and 2,3- dihydrobenzofuran-3-yl. This definition also applies to heterocyclyl as part of a composite substituent, for example heterocyclylalkyl etc., unless defined elsewhere.

Optionally substituted groups may be mono- or polysubstituted, where the substituents in the case of polysubstitutions may be identical or different.

Not included are combinations which are against natural laws and which the person skilled in the art would therefore exclude based on his/her expert knowledge. Ring structures having three or more adjacent oxygen atoms, for example, are excluded.

In step A) of the process according to the invention an imidazole of formula (II)

is reacted with a ketone of formula (III),

to yield a compound of formula (IV)

R¹, R² and R³ are defined as outlined above. It is preferred to react the imidazole of formula (II) and the ketone of formula (III) in a molar ratio of 1 : 0.5 to 1 : 5, preferably 1 : 0.7 to 1 : 4, more preferred 1 : 0.9 to 1 : 3, even more preferred 1 : 1 to 1 : 2, and most preferred 1 : 1.05 to 1 : 1.5.

It is preferred to perform step A) of the process according to the invention in the presence of a solvent, more preferred in the presence of a solvent selected from acetonitrile, acetone, diethyl ether, cyclopentyl methyl ether, /c/7-butyl methyl ether, tetrahydrofuran, methyltetrahydrofuran, in particular 2- methyltetrahydrofuran, toluene, V-methyl-2-pyrrolidone (NMP), dimethylformamide (DMF) and mixtures thereof, most preferred in the presence of acetonitrile or acetone.

The preferred amount of solvent present in step A) varies depending inter alia from the solvent used and the solubility of the respective imidazole of formula (II) and ketone of formula (III) in said solvent. Generally, the amount of solvent shall be sufficient to fully dissolve imidazole of formula (II) and ketone of formula (III) under the reaction conditions. Suitable amounts can be easily determined by one skilled in the art via solubility tests. Preferably, the weight ratio of solvent to combined amounts of imidazole of formula (II) and ketone of formula (III) is 1 : 1 to 1000 : 1, more preferred 3 : 1 to 500 : 1, more preferred 5 : 1 to 100 : 1, most preferred 5 : 1 to 20 : 1. Step A) is preferably carried out in the presence of a base. These preferably include alkali metal or alkaline earth metal acetates, amides, carbonates, hydrogencarbonates, hydrides, hydroxides or alkoxides, for example sodium acetate, potassium acetate or calcium acetate, lithium amide, sodium amide, potassium amide or calcium amide, sodium carbonate, potassium carbonate or calcium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate or calcium hydrogencarbonate, lithium hydride, sodium hydride, potassium hydride or calcium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, n-butyllithium, sec-butyllithium, tert-butyllithium, lithium diisopropylamide, lithium bis(trimethylsilyl)amide, sodium methoxide, ethoxide, n- or i-propoxide, h-, i-, s- or t-butoxide or potassium methoxide, ethoxide, n- or i-propoxide, n-, i-, s- or t-butoxide; and also basic organic nitrogen compounds, for example trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldiisopropylamine, N,N-dimethylcyclohexylamine, dicyclohexylamine, ethyldicyclohexylamine, N,N- dimethylaniline, N,N-dimethylbenzylamine, pyridine, 2-methyl-, 3 -methyl-, 4-methyl-, 2,4-dimethyl-, 2,6- dimethyl-, 3,4-dimethyl- and 3,5-dimethylpyridine, 5-ethyl-2-methylpyridine, 4-dimethylaminopyridine, N-methylpiperidine, l,4-diazabicyclo[2.2.2]-octane (DABCO), l,5-diazabicyclo[4.3.0]-non-5-ene (DBN) or l,8-diazabicyclo[5.4.0]-undec-7-ene (DBU).

Preferably, the base is selected from Na2CC>3, K₂CO₃, CS₂CO₃, NaOH, KOH, NaOMe, KOMe, KOtBu, NaH and mixtures thereof, more preferably from Na2CC>3, K₂CO₃, CS₂CO₃ and mixtures thereof. Particular preferred the base is Na2CC>3 or K₂CO3.

The preferred amount of base present in step A) may vary within broad limits. However, generally the preferred molar ratio of base to imidazole of formula (II) is 1 : 1 to 10 : 1, more preferred 1.1 : 1 to 5 : 1, more preferred 1.2 : 1 to 2 : 1, most preferred 1.2 : 1 to 1.5 : 1.

Preferably, step A) is carried out at a temperature of 0°C to 50°C, more preferred l0°C to 40°C, and most preferred 20°C to 30°C.

The reaction time of step A) of the process according to the invention varies depending on the scale of the reaction and the reaction temperature, but is generally between a few, e.g. 5, minutes and 48 hours.

Step A) is generally performed under standard pressure (1 atm). However, it is also possible to work under elevated or reduced pressure.

The resulting reaction mixture comprising the compound of formula (IV) can be directly used in step B) of the present invention. However, it is preferred to work-up the reaction mixture by procedures generally known in the art. This allows isolation and purification of the compound of formula (IV) before further processing of said compound in step B) of the process according to the invention.

Preferably, any solvent present in the reaction mixture is removed, water is added to form a suspension, the resulting suspension is stirred and the solid filtered. Preferably, the solid is washed with water and dried. Generally, the resulting product is of high purity and perfectly suitable for further processing in step B) of the process according to the invention. If desired, the resulting product may be further purified by known techniques, for example recrystallization or chromatography.

Imidazoles of formula (II) and ketones of formula (III) are either readily available from commercial sources or obtainable by known methods. The imidazoles of formula (II) can be for example obtained by alkaline hydrolysis of the respective 4,5-dicyanoimidazoles as disclosed in J.P. Ferris et al., J. Org. Chem. 1987, 52, 2355-2361 and P.K. Bridson et al., Heterocycles, 1995, 41, 1271-1274, or in analogy to the methods described therein.

In one preferred embodiment of the process according to the invention, the imidazoles of formula (II) are obtained by reacting a compound of formula (VI)

(VI), wherein

R² is defined as in formula (I), with an aqueous alkali metal hydroxide solution, preferably aqueous sodium hydroxide. The preferred, more preferred and most preferred definitions given above for R² apply mutatis mutandis.

The reactants are known compounds that are readily available from commercial sources or can be prepared according to well established methods.

It is preferred to react the 4,5-dicyanoimidazole of formula (VI) and the alkali metal hydroxide in a molar ratio of 1 : 1 to 1 : 5, preferably 1 : 1.5 to 1 : 4, and most preferred 1 : 2 to 1 : 3. Preferably, a 0.5 to 2 molar aqueous alkali metal hydroxide solution is used, more preferred a 0.5 to 2 molar aqueous sodium hydroxide solution, and most preferred a 0.8 to 1.2 molar aqueous sodium hydroxide solution.

Preferably, this reaction is carried out at a temperature of 20°C to 90°C, more preferred 20°C to 80°C, more preferred 25°C to 70°C, and most preferred 25°C to 50°C. The reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a few, e.g. 5, minutes and 48 hours.

This step is generally performed under standard pressure (1 atm). However, it is also possible to work under elevated or reduced pressure.

The resulting reaction mixture comprising the compound of formula (II) can be directly used in step A) of the present invention. However, it is preferred to work-up the reaction mixture by procedures generally known in the art. This allows isolation and purification of the compound of formula (II) before further processing of said compound in step A) of the process according to the invention.

Preferably, the pH (23°C, 1 atm) of the reaction mixture is adjusted to a value of 3 to 8, preferably 4 to 7, more preferred 5 to 7, most preferred 5.5 to 6.5 by addition of an acid. Preferably, the acid is selected from hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, trifluoromethanesulfonic acid, 4-methylbenzenesulfonic acid and mixtures thereof, preferably from hydrochloric acid and sulfuric acid, more preferred hydrochloric acid. Most preferred the pH value is adjusted by addition of concentrated hydrochloric acid.

Preferably, the resulting suspension is filtered, the solid washed with water and dried. Generally, the resulting product is of high purity and perfectly suitable for further processing in step A) of the process according to the invention. If desired, the resulting product may be further purified by known techniques, for example recrystallization or chromatography.

In step B) of the process according to the invention the compound of formula (IV)

wherein

R¹ and R² are defined as in formula (I), is converted into the desired compound of formula (I) by cleavage of the carbamoyl group.

Such cleavage can be achieved by different methods, for example by heating the compound of formula (IV) in an acidic environment and/or in the presence of a catalyst promoting replacement of the carbamoyl group by a hydrogen atom.

Preferably, the cleavage of the carbamoyl group from the compound of formula (IV) in step B) is performed by treating the compound of formula (IV) in a first step Bl) with an acid selected from hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, trifluoromethanesulfonic acid, 4-methylbenzenesulfonic acid and mixtures thereof, to yield a carboxylic acid of formula (V),

wherein

R¹ and R² are defined as in formula (I), and heating in a further step B2) the carboxylic acid of formula (V) in the presence of an organic solvent having a boiling point at 1 bar of from 90 °C to 300 °C or mixtures thereof, to a temperature of from 50

°C to 250 °C.

The conversion of a carbamoyl substituent of an imidazole ring to the respective carboxyl group under acidic conditions is generally known and described by N.B. Maximov et al. in Synthesis 2011, 9, 1465- 1471 and M. Skinner et al. in ACS Macro Lett. 2017, 6, 215-218. N.B. Maximov et al. further report conversion of an also present cyano substituent to a carboxyl group under the specific conditions described in said reference. Surprisingly, no such conversion of the cyano group is observed in step Bl) of the process according to the present invention.

Preferably, the acid used in step Bl) is selected from hydrochloric acid and sulfuric acid, more preferred the acid is sulfuric acid. Preferably, the acid used in step Bl) is present as aqueous solution, more preferred the acid used in step

Bl) is aqueous sulfuric acid, preferably an aqueous sulfuric acid comprising 10 to 80 % by weight H2SO4, preferably 20 to 70 % by weight H2SO4, more preferred 30 to 60 % by weight H2SO4, more preferred 35 to 50 % by weight H2SO4, most preferred 35 to 45 % by weight H2SO4.

The amount of acid present in step Bl) may vary within broad limits depending in particular from the specific acid used and the reaction temperature. However, generally the preferred molar ratio of acid to compound of formula (IV) is 1 : 1 to 100 : 1, more preferred 2 : 1 to 80 : 1, more preferred 3 : 1 to 70 : 1, more preferred 4 : 1 to 60 : 1, most preferred 5 : 1 to 50 : 1.

Preferably, step Bl) is carried out at a temperature of 20°C to l00°C, more preferred 40°C to 99°C, more preferred 60°C to 97°C, and most preferred 80°C to 90°C. The reaction time of step Bl) varies depending on the scale of the reaction and the reaction temperature, but is generally between a few, e.g. 5, minutes and 48 hours, preferably between 1 and 24 hours. Step Bl) is generally performed under standard pressure (1 atm). However, it is also possible to work under elevated or reduced pressure.

The resulting reaction mixture comprising the compound of formula (V) can be directly used in step B2) of the present invention. However, it is preferred to work-up the reaction mixture by procedures generally known in the art. This allows isolation and purification of the compound of formula (V) before further processing of said compound in step B2) of the process according to the invention.

Preferably, the reaction mixture is cooled to a temperature of from 0 °C to 30 °C, preferably 0 °C to 10 °C, for example by pouring the reaction mixture into ice water. Preferably, the cooled reaction mixture is stirred and the resulting suspension filtered. Preferably, the solid is washed with water and dried. Generally, the resulting product is of high purity and perfectly suitable for further processing in step B2) of the process according to the invention. If desired, the resulting product may be further purified by known techniques, for example recrystallization or chromatography.

In step B2) the carboxylic acid of formula (V) is heated to a temperature of from 50 °C to 250 °C in the presence of an organic solvent having a boiling point at 1 bar of from 90 °C to 300 °C or mixtures thereof. Such treatment results in the cleavage of the carboxyl group and formation of a compound of formula

CD-

Cleavage of a carboxyl substituent from an imidazole ring at elevated temperatures is generally known and described by J.P. Collman et al. in Journal of Fluorine Chemistry, 2000, 201, 189-197.

Preferably, in step B2) the carboxylic acid of formula (V) is heated to a temperature of from 70 °C to 200 °C, more preferred 90°C to l80°C, more preferred l00°C to l50°C, most preferred 1 l0°C to l30°C.

Preferably, the temperature is below the boiling point of the organic solvent(s) present in step B2). However, it is also possible that the temperature is above said boiling point. In the latter case the reaction needs to be performed under suitable conditions, like reflux or elevated pressure, for example in an autoclave.

Preferably, in step B2) of the process according to the invention the organic solvent is selected from nitrobenzene, dimethylformamide, _/V,_/V-dimcthylacctamidc, dimethyl sulfoxide, propylene carbonate, acetic anhydride and mixtures thereof. Particularly preferred the organic solvent is acetic anhydride.

The preferred amount of solvent present in step B2) varies depending inter alia from the solvent used and the solubility of the respective compound of formula (V) in said solvent. Generally, the amount of solvent shall be sufficient to fully dissolve the compound of formula (V) under the reaction conditions. Suitable amounts can be easily determined by one skilled in the art via solubility tests. Preferably the weight ratio of solvent to amount of compound of formula (V) is 1 : 1 to 1000 : 1 , more preferred 1 : 1 to 500 : 1, more preferred 2 : 1 to 100 : 1, most preferred 2 : 1 to 10 : 1.

The reaction time of step B2) of the process according to the invention varies depending on the scale of the reaction and the reaction temperature, but is generally between a few, e.g. 5, minutes and 48 hours.

Step B2) is generally performed under standard pressure (1 atm). However, it is also possible to work under elevated or reduced pressure.

The resulting reaction mixture comprising the compound of formula (I) can be directly used as such. However, it is preferred to work-up the reaction mixture by procedures generally known in the art. This allows isolation and purification of the compound of formula (I) before any further processing of said compound.

Preferably, any solvent present in the reaction mixture is removed, the remaining product dissolved in a suitable solvent, for example toluene, and the solvent removed again. Generally, the resulting product is of sufficient purity. If desired, the resulting product may be further purified by known techniques, for example recrystallization or chromatography.

In a preferred embodiment of step B2) the crude reaction mixture resulting from heat treatment of the carboxylic acid of formula (V) is treated with oxalic acid, preferably a solution of oxalic acid in an organic solvent, preferably an ether, particularly preferred /c/7-butyl methyl ether. The resulting mixture is than stirred until a precipitate has been formed, and the precipitate isolated, preferably by filtration. Preferably, the isolated precipitate is washed with an organic solvent, preferably an ether, particularly preferred ieri-butyl methyl ether, and the washed solid suspended in an organic solvent, preferably an ether, particularly preferred teri-butyl methyl ether. The suspension is treated with a base, preferably an alkaline carbonate or hydrogen carbonate, particularly preferred sodium carbonate, potassium carbonate sodium hydrogen carbonate, potassium hydrogen carbonate or a mixture thereof. Preferably, an aqueous solution of the base is used. Resulting phases are separated and the desired compound of formula (I) isolated from the organic phase. This particular work-up provides the compounds of formula (I) in particular high purity.

As outlined above, compounds of formula (I) are valuable intermediates in the synthesis of compounds useful in the field of crop protection, in particular the fungicides disclosed in WO 2016/156290 Al .

In a particular aspect the present invention refers to a process, wherein a compound of formula (I) is synthesized as outlined above and is further reacted to a fungicide using process M disclosed in WO 2016/156290 Al . In another particular aspect the present invention refers to a process, wherein a compound of formula (I) is synthesized as outlined above and is further reacted to a fungicide of formula (VII)

wherein R¹ is defined as in formula (I);

R⁴ represents hydrogen or Ci-Cs-alkyl;

R⁵ represents hydrogen or Ci-Cs-alkyl; or R⁴ and R⁵ form together with the carbon atom to which they are attached a C3-C7-cycloalkyl, wherein the C3-C7-cycloalkyl ring is non-substituted or substituted by one or more Ci-C4-alkyl group(s); and Q represents a 6-membered aromatic cycle of formula (Q-I)

(Q-i), wherein

U¹ represents CX¹ or N;

U² represents CX² or N;

U³ represents CX³ or N;

U⁴ represents CX⁴ or N;

U⁵ represents CX⁵ or N; wherein X¹, X², X³, X⁴, and X⁵ independently from each other represent hydrogen, halogen, nitro, cyano, sulfanyl, pentafluoro-k⁶-sulfanyl, Ci-Cs-alkyl, Ci-Cs-haloalkyl having 1 to 5 halogen atoms, Cs-Cs-cycloalkyl, C₃-C₇-halocycloalkyl having 1 to 5 halogen atoms, Ci-Cs- haloalkyl-C₃-C₇-cycloalkyl, C₃-C₇-cycloalkenyl, C₂-Cs-alkenyl, C₂-Cs-alkynyl, C₆-C₁₂- bicycloalkyl, C₃-C₈-cycloalkyl-C₂-Cs-alkenyl, C₃-Cs-cycloalkyl-C₂-C₈-alkynyl, Ci-Cx-alkoxy, Ci-C₈-haloalkoxy having 1 to 5 halogen atoms, Ci-Cs-alkoxycarbonyl, Ci-Cs- haloalkoxycarbonyl, Ci-Cx-alkylsulfcnyl, C₂-C₈-alkenyloxy, C₃-C₈-alkynyloxy, C₃-C₆- cycloalkoxy, Ci-Cx-alkylsulfmyl, Ci-Cs-alkylsulfonyl, tri(Ci-C₈-alkyl)-silyloxy, tri(Ci-C₈- alkyl)-silyl, tri(Ci-C₈-alkyl)-silyl-C₂-C₈-alkynyl, tri(Ci-C₈-alkyl)-silyl-C₂-C₈-alkynyloxy, aryl, aryloxy, arylsulfenyl, heteroaryl, heteroaryloxy, wherein the aryl, aryloxy, arylsulfenyl, heteroaryl, heteroaryloxy is non-substituted or substituted by one or more group(s) selected from halogen, cyanosulfanyl, pentafluoro-l⁶- sulfanyl, Ci -Cx-alkyl, Ci-Cs-haloalkyl, Ci-Cs-cyanoalkyl, Ci-Cx-alkyloxy, Ci-Cs- haloalkyloxy, tri(Ci-C₈-alkyl)silyl, tri(Ci-C₈-alkyl)silyl-Ci-C₈-alkyl, C₃-C₇-cycloalkyl, C₃-C₇- halocycloalkyl, C₃-C₇-cycloalkenyl, C₃-C₇-halocycloalkenyl, C₄-Cio-cycloalkylalkyl, C₄-C₁₀- halocycloalkylalkyl, C₆-Ci₂-cycloalkylcycloalkyl, Ci-C₈-alkyl-C₃-C₇-cycloalkyl, Ci-Cs- alkoxy-C₃-C₇-cycloalkyl, tri(Ci-C₈-alkyl)silyl-C₃-C₇-cycloalkyl, C₂-C₈-alkenyl, C₂-C₈- alkynyl, C₂-C₈-alkenyloxy, C₂-C₈-haloalkenyloxy, C₃-C₈-alkynyloxy, C₃-C₈-haloalkynyloxy, Ci-C₈-cyanoalkoxy, C₄-C₈-cycloalkylalkoxy, C₃-C₆-cycloalkoxy, Ci-Cs-atkylsulfanyl, Ci-Cs- haloalkylsulfanyl, Ci-Ck-alkylsulfinyl, Ci-CVhaloalkylsulfmyl, Ci-Cs-alkylsulfonyl, Ci-Cs- haloalkylsulfonyl, Ci-Ck-alkylsulfonyloxy, Ci-Ck-haloalkylsulfonyloxy, Ci-Cs-alkoxyalkyl, Ci-C₈-alkylthioalkyl, Ci-Ck-alkoxyalkoxyalkyl, Ci-Cs-haloalkoxyalkyl, benzyl, phenyl, 5- membered heteroaryl, 6-membered heteroaryl, 6-membered heteroaryloxy, benzyloxy, phenyloxy, benzylsulfanyl, and phenylsulfanyl, wherein the benzyl, phenyl, 5-membered heteroaryl, 6-membered heteroaryl, 6-membered heteroaryloxy, benzyloxy, phenyloxy, benzylsulfanyl and phenylsulfanyl is non-substituted or substituted by one or more group(s) selected from halogen, CN, nitro, Ci-Cs-alkyl, C₁-C₄- haloalkyl, Ci-C₄-alkoxy, Ci-C₄-haloalkoxy and pentafluoro-l⁶-sulfanyl; and wherein at most two of U¹, U², U³, U⁴ and U⁵ represent N; or

U¹ and U² or U² and U³ or U³ and U⁴ form together an additional saturated or unsaturated 4 to 6-membered halogen- or Ci-CValkyl-substitutcd or non-substituted ring; wherein the compound of formula (I) is reacted with a manganese compound of formula (VIII),

wherein each X, Y and Z represents independently from each other halogen;

M¹ represents Mg or Zn; n is 1 or 2; m is 0 or 1 ; n+m is 2;

0 < z¹ < 10;

0 < z² < 10; and R⁴, R⁵ and Q are defined as in formula (VII).

As outlined above R¹ is defined as in formula (I). The preferred, more preferred and most preferred definitions given with regard to formula (I) apply mutatis mutandis.

An arrow, as in formula (Q-I), depicts the bonding position of the shown moiety to the remainder of the molecule. R⁴ preferably represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or /c/7-butyl.

R⁴ more preferably represents hydrogen, methyl or ethyl.

R⁴ most preferably represents hydrogen.

R⁵ preferably represents hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or /c/7-butyl.

R⁵ more preferably represents hydrogen, methyl or ethyl. R⁵ most preferably represents hydrogen.

R⁴ and R⁵ may form together with the carbon atom to which they are attached an optionally Ci-C₄-alkyl- substituted C₃-C₇-cycloalkyl ring. In such embodiment R⁴ and R⁵ preferably form together with the carbon atom to which they are attached a non-substituted C3-C6-cycloalkyl ring, more preferably a non-substituted CXCk -cycloalkyl ring, most preferably a cyclopropyl ring.

Q preferably represents a substituted 6-membered aromatic heterocycle containing one or two nitrogen atoms or a substituted 6-membered aromatic carbocycle. Substituted meaning that the cycle of the given formula comprises at least one of X¹, X², X³, X⁴ or X⁵ not being hydrogen.

Q also preferably represents a, preferably substituted, 6-membered aromatic cycle of formula (Q-I-l) to (Q-I-10)

wherein X¹, X², X³, X⁴ and X⁵ have the same definition as given above. Preferred definitions of X¹, X², X³, X⁴ and X⁵ are given below.

Q more preferably represents a, preferably substituted, phenyl, 3-pyridyl or 4-pyridyl of formula (Q-I- 1) to (Q-I-3)

wherein X¹, X², X³, X⁴ and X⁵ have the same definition as given above. Preferred definitions of X¹, X², X³, X⁴ and X⁵ are given below. Q more preferably represents a, preferably substituted, phenyl or 3-pyridyl of formula (Q-I-l) or (Q-I-

2)

Q most preferably represents a, preferably substituted, phenyl of formula (Q-I-l)

X¹, X², X³, X⁴, and X⁵ independently from each other preferably represent hydrogen, halogen, nitro, cyano, sulfanyl, pentafluoro^⁶-sulfanyl, Ci-Cs-alkyl, Ci-Cs-haloalkyl having 1 to 5 halogen atoms, C₃-C₈- cycloalkyl, C₃-C₇-halocycloalkyl having 1 to 5 halogen atoms, Ci-Cs-haloalkyl-C₃-C₇-cycloalkyl, C₃-C₇-cycloalkenyl, C₂-Cs-alkenyl, C₂-Cs-alkynyl, C₆-Ci₂-bicycloalkyl, C₃-Cs-cycloalkyl-C₂-C₈- alkenyl, C₃-C₈-cycloalkyl-C₂-C₈-alkynyl, Ci-Cx-alkoxy, Ci-Cx-haloalkoxy having 1 to 5 halogen atoms, Ci-C₈-alkoxycarbonyl, Ci-Cs-haloalkoxycarbonyl, Ci -Cx-alky lsulfcnyl, C₂-C₈-alkenyloxy, C₃-C₈-alkynyloxy, C₃-C₆-cycloalkoxy, C ₁ -CX-al ky lsu lfiny 1, Ci-Cs-alkylsulfonyl, tri(Ci-C₈-alkyl)- silyloxy, tri(Ci-C₈-alkyl)-silyl, tri(Ci-C₈-alkyl)-silyl-C₂-C₈-alkynyl, tri(Ci-C₈-alkyl)-silyl-C₂-C₈- alkynyloxy, C₆-Ci₄-aryl, C₆-Ci₄-aryloxy, C₆-Ci₄-arylsulfenyl, 5- or 6-membered heteroaryl, or 5- or 6-membered heteroaryloxy, wherein the C₆-Ci₄-aryl, C₆-Ci₄-aryloxy, C₆-Ci₄-arylsulfenyl, 5- or 6-membered heteroaryl, and 5- or 6-membered heteroaryloxy is non-substituted or substituted by one or more group(s) selected from halogen, cyanosulfanyl, pentafluoro^⁶-sulfanyl, Ci -Cx-alkyl, Ci-Cx-haloalkyl, Ci-Cx-cyanoalkyl, Ci-Cs-alkyloxy, Ci-Cx-haloalkyloxy, tri(Ci-C₈-alkyl)silyl, tri(Ci-C₈-alkyl)silyl-Ci-C₈-alkyl, C₃-C₇- cycloalkyl, C₃-C₇-halocycloalkyl, C₃-C₇-cycloalkenyl, C₃-C₇-halocycloalkenyl, C₄-C₁₀- cycloalkylalkyl, C₄-Cio-halocycloalkylalkyl, C₆-Ci₂-cycloalkylcycloalkyl, Ci-C₈-alkyl-C₃-C₇- cycloalkyl, Ci-C₈-alkoxy-C₃-C₇-cycloalkyl, tri(Ci-C₈-alkyl)silyl-C₃-C₇-cycloalkyl, C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₂-Cs-al enyloxy, C₂-Cs-haloalkenyloxy, C₃-Cs-alkynyloxy, C₃-C₈-haloalkynyloxy, Ci-C₈-cyanoal oxy, C₄-C₈-cycloalkylalkoxy, C₃-C₆-cycloalkoxy, C_l -Cx-alky lsulfanyl, Ci-Cs- haloalkylsulfanyl, Ci-Cx-alkylsulfinyl, Ci-Cx-haloalkylsulfmyl, Ci-Cx-alkylsulfonyl, Ci-Cs- haloalkylsulfonyl, Ci -Cx-alky lsulfonyloxy, Ci-Cx-haloalkylsulfonyloxy, Ci-Cx-alkoxyalkyl, Ci-Cs- alkylthioalkyl, Ci-Cx-alkoxyalkoxyalkyl, Ci-Cx-haloalkoxyalkyl, benzyl, phenyl, 5-membered heteroaryl, 6-membered heteroaryl, 6-membered heteroaryloxy, benzyloxy, phenyloxy, benzylsulfanyl, and phenylsulfanyl.

X¹, X², X³, X⁴, and X⁵ independently from each other more preferably represent hydrogen, halogen, nitro, cyano, sulfanyl, pentafluoro^⁶-sulfanyl, Ci-Cs-alkyl, C₃-Cs-cycloalkyl, Ci-Cs-alkoxy, Ci-Cs- alkoxycarbonyl, Ci-C₆-alkylsulfenyl, or C₃-C₆-cycloalkoxy.

X¹, X², X³, X⁴, and X⁵ independently from each other more preferably represent hydrogen, halogen, Ci-Cs- alkyl, C₃-C₈-cycloalkyl or Ci-Cs-alkoxy.

X¹, X², X³, X⁴, and X⁵ independently from each other more preferably represent hydrogen, fluorine, chlorine, bromine, Ci-C₄-atkyl, C₃-C₅-cycloalkyl or Ci-C₄-alkoxy.

X¹, X², X³, X⁴, and X⁵ independently from each other more preferably represent hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, /c/7-butyl, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, or tert- butoxy.

X¹, X², X³, X⁴, and X⁵ independently from each other more preferably represent hydrogen, fluorine, chlorine, bromine, methyl, cyclopropyl, or methoxy.

X¹ most preferably represents hydrogen or fluorine.

X² most preferably represents hydrogen or chlorine.

X³ most preferably represents hydrogen, fluorine or methoxy.

X⁴ most preferably represents hydrogen, fluorine, chlorine, methyl or methoxy.

X⁵ more preferably represents hydrogen, fluorine, bromine or cyclopropyl, most preferably fluorine.

Particular preference is given to those cases in which each of the symbols have the abovementioned more and/or most preferred definitions. Hence, particular preferred is a process, wherein a compound of formula (I) is synthesized as outlined above and is further reacted to a fungicide of formula (VII), wherein the compound of formula (VII) is represented by formula (Vila)

(Vila), wherein R¹ represents Ci-Cs-alkyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₃-C₇-cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci- C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₆-Ci₄-aryl, and

X¹ , X² , X³ , X⁴ and X⁵ independently from each other represent hydrogen, halogen, Ci-Cs-alkyl, C₃-C₈- cycloalkyl or Ci-Cs-alkoxy.

R¹ preferably represents Ci-C₄-alkyl, optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci- C₄-haloalkoxy-, Ci-C₄-alkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₃-C₆-cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted phenyl. R¹ more preferably represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, /c/7-butyl, cyclopropyl, 1 -halocyclopropyl, l-(Ci-C₄-alkyl)cyclopropyl, or optionally halogen-substituted phenyl.

R¹’ most preferably represents isobutyl, teri-butyl, cyclopropyl, 1 -chlorocyclopropyl, 1- fluorocyclopropyl, 1 -methylcyclopropyl, phenyl or 2,4-difluorophenyl. X¹ , X² , X³ , X⁴ , and X⁵ independently from each other preferably represent hydrogen, fluorine, chlorine, bromine, Ci-C4-alkyl, CYCYcycloalkyl or Ci-C4-alkoxy.

X¹ , X² , X³ , X⁴ , and X⁵ independently from each other more preferably represent hydrogen, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, /c/7-butyl, cyclopropyl, cyclobutyl, cyclopentyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, or tert- butoxy.

X¹ , X² , X³ , X⁴ , and X⁵ independently from each other more preferably represent hydrogen, fluorine, chlorine, bromine, methyl, cyclopropyl, or methoxy.

X¹ most preferably represents hydrogen or fluorine.

X² most preferably represents hydrogen or chlorine.

X³ most preferably represents hydrogen, fluorine or methoxy.

In this aspect of the invention the compound of formula (I) is reacted with a manganese compound of formula (VIII)

X, Y, and Z independently from each other preferably represent chlorine, bromine or iodine, more preferably chlorine or bromine. n is either 1 or 2.

In case n is 1, m is 1, i.e. the manganese compound comprises one organic moiety per manganese atom.

In case n is 2, m is 0, i.e. the manganese compound comprises two organic moieties per manganese atom. M¹ preferably represents Mg. z¹ can be any number in the range of 0 to 10. If z¹ is greater than 0, M ' X2 is present and can form a complex with the manganese moiety and optionally present LiZ. Preferably the following equation applies: 0 < z¹ < 5, preferably 0 < z¹ < 3, more preferred 0 < z¹ < 2. Also z² can be any number in the range of 0 to 10. However, preferably z² is greater than 0, i.e. at least some LiZ is present. Preferably the following equation applies: 0 < z² < 5, preferably 0 < z² < 3, more preferred 0 < z² < 2.

The compound of formula (I) and the manganese compound of formula (VIII) are preferably reacted in a molar ratio of 1 : 0.4 to 1 : 5, more preferred 1 : 0.5 to 1 : 4, most preferred 1 : 0,55 to 1 : 3.

In case the manganese compound of formula (VIII) used is a manganese compound of formula (VIII), wherein n is 1 and m is 1, the molar ratio of compound of formula (I) to manganese compound of formula (VIII) is preferably 1 : 1 to 1 : 5, more preferred 1 : 1.5 to 1 : 4, even more preferred 1 : 1.7 to 1 : 3, most preferred 1 : 2 to 1 : 2.5.

In case the manganese compound of formula (VIII) used is a manganese compound of formula (VIII), wherein n is 2 and m is 0, the molar ratio of compound of formula (I) to manganese compound of formula (VIII) is preferably 1 : 0.4 to 1 : 3, more preferred 1 : 0.5 to 1 : 2, even more preferred 1 : 0.6 to 1 : 1, most preferred 1 : 0.7 to 1 : 0.8.

It is preferred to perform this step in the presence of a solvent, preferably in the presence of an aprotic solvent, more preferably a solvent selected from tetrahydrofuran, methyltetrahydrofuran, in particular 2- methyltetrahydrofuran, diethylether, cyclopentyl methyl ether, /c/7-butyl methyl ether, toluene, N- methylpyridione (NMP), dimethylformamide (DMF) and mixtures thereof, most preferably selected from diethyl ether, ieri-butyl methyl ether, tetrahydrofuran, toluene, and mixtures thereof.

Preferably, this step is carried out at a temperature of -l0°C to 50°C, more preferred -l0°C to 30°C, and most preferred -5°C to 20°C.

The reaction time of this step varies depending on the scale of the reaction and the reaction temperature, but is generally between a few, e.g. 5, minutes and 48 hours.

Preferably, the resulting reaction mixture is quenched with water or an aqueous ammonium halogenide solution, preferably an aqueous NH₄CI solution, preferably a saturated aqueous NH₄CI solution.

Manganese compounds of formula (VIII) can be obtained as disclosed in P. Knochel et al., Synlett 2015, 26, 514-518 and WO 2007/113294 Al or in analogy to the methods described therein.

In one preferred embodiment the manganese compounds of formula (VIII) are obtained by the reaction of a compound of formula (IX)

(ix), wherein R , R , Q and X are defined as in formula (VIII), and a manganese halogenide of formula (X)

MnY

² (X), wherein each Y is defined as in formula (VIII), in the presence of magnesium and LiZ, wherein Z is defined as in formula (VIII).

The preferred, more preferred and most preferred definitions given above for R⁴, R⁵, Q, X, Y, and Z apply mutatis mutandis.

This reaction is preferably conducted under a protective atmosphere, preferably nitrogen or argon atmosphere.

Preferably, the reaction is carried out in the presence of an aprotic solvent, preferably selected from tetrahydrofuran, methyltetrahydrofuran, in particular 2-methyltetrahydrofuran, diethylether, cyclopentyl methyl ether, /c/7-butyl methyl ether, toluene, and mixtures thereof, most preferably selected from diethyl ether, tetrahydrofuran, toluene and mixtures thereof. Preferably, any solvent present in the reaction is dried before use.

Preferably, the reaction is carried out in the presence of an activating agent selected from copper salts, nickel salts, iron compounds, cobalt compounds, h, C₂H₄Br₂, Cl(CH₂)₂Br, tert.- BuOLi, BCfi, BF₃, L1BH₄, L1AIH₄, NaAlH₄, Et₃Al, DIBAL-H (diisobutyl aluminum hydride), Na[H₂Al(OCH₂CH₂OCH₃)], Me₃SiCl, Et₂Zn, IC1, SnCT and mixtures thereof, preferably selected from I₂, C₂H₄Br₂, Cl(CH₂)₂Br, tert. - BuOLi, BCI₃, BF₃, L1BH₄, L1AIH₄, NaAIFU, Et₃Al, DIBAL-H (diisobutyl aluminum hydride), Na[H₂Al(0CH₂CH₂0CH₃)], Me-, Si Cl, Et₂Zn, IC1, SnCT and mixtures thereof. Particularly preferred the reaction is carried out in the presence of T, C₂H₄Br₂, diisobutyl aluminum hydride, or Me₃SiCl.

The reaction is preferably conducted at a temperature of from -10 to 30 °C, more preferred -5°C to 5 °C, and a pressure of from 0.5 to 2 bar. Preferably, the compound of formula (IX) and the manganese halogenide of formula (X) are reacted in a molar ratio of 1 : 0.4 to 1 : 1, more preferred 1 : 0.5 to 1 : 0.8, most preferred about 1 : 0.55 to 1 : 0.7.

Preferably, the manganese halogenide of formula (X) and LiZ are present in a molar ratio of 1 : 0.5 to 1 : 2, more preferred 1 : 0.7 to 1 : 1.5, most preferred about 1 : 0.8 to 1 : 1.2. Preferably, the compound of formula (IX) and magnesium are present in a molar ratio of 1 : 1 to 1 : 2, more preferred 1 : 1 to 1 : 1.5, most preferred about 1 : 1.1 to 1 : 1.3.

The reaction mixture resulting from the reaction of the compound of formula (IX) and the manganese halogenide of formula (X) can be worked-up by procedures generally known in the art, e.g. by evaporation of any organic solvent, preferably under reduced pressure. If desired, the resulting manganese compounds of formula (VIII) may be further purified by known techniques, for example crystallization. However, preferably the resulting reaction mixture comprising the manganese compound of formula (VIII) is directly used in the preparation of a compound of formula (VII).

In another preferred embodiment the manganese compounds of formula (VIII) are obtained by reacting a Grignard compound of formula (XI)

(xi), wherein R⁴, R⁵, Q and X are defined as in formula (VIII), and a manganese lithium complex of formula (XII)

MnY₂ z³ LiZ (XII), wherein Y and Z are defined as in formula (VIII); and z³ is 0, 1, 2, 3, 4 or 5.

The preferred, more preferred and most preferred definitions given above for R⁴, R⁵, Q, X, Y, and Z apply mutatis mutandis. z³ is preferably 1 , 2 or 3, more preferably 1 or 2, and most preferably 2. The reactants are known compounds that are readily available from commercial sources or can be prepared according to well established methods. For example, the Grignard compound of formula (XI) can be obtained by reacting the respective halogenide of formula (IX) and magnesium, preferably magnesium turnings, preferably in the presence of an activating reagent like copper salts, nickel salts, iron compounds, cobalt compounds, F, C₂H₄Br₂, Cl(CH₂)₂Br, ter/.-BuOLi, BCF, BF₃, L1BH₄, L1AIH₄, NaAlH₄, Et₃Al, DIBAL-H (diisobutyl aluminum hydride), Na[H₂Al(0CH₂CH₂0CH₃)], Mc-.SiCI, Et₂Zn, IC1, SnCF and mixtures thereof, preferably I₂, C₂H₄Br₂, Cl(CH₂)₂Br, tert- BuOLi, BC1₃, BF₃, LiBH₄, L1AIH₄, NaAlH₄, Et₃Al, DIBAL-H (diisobutyl aluminum hydride), Na[H₂Al(0CH₂CH₂0CH₃)], Me₃SiCl, Et₂Zn, IC1, SnCF and mixtures thereof, more preferred 1 ,2-dibromoethane, and an aprotic solvent, preferably selected from tetrahydrofuran, methyltetrahydrofuran, in particular 2-methyltetrahydrofuran, diethylether, cyclopentyl methyl ether, ieri-butyl methyl ether, toluene, and mixtures thereof, most preferably selected from diethyl ether, tetrahydrofuran, toluene and mixtures thereof. Preferably, any solvent is dried before use.

Generally, one may work-up the reaction product resulting from the synthesis of the Grignard compound of formula (XI) for example in order to isolate, concentrate, dilute or purify the Grignard compound or a solution or suspension thereof. However, it is preferred to directly use the Grignard compound in the further reaction with the manganese lithium complex of formula (XII) without any treatment like isolation or purification.

The Grignard reagent is represented by formula (XI). However, as generally known to the skilled person, Grignard compounds undergo solvent-dependent equilibrium between different magnesium compounds that can be described by the so-called Schlenck equilibrium. The Schlenck equilibrium for the Grignard reagent according to formula (XI) can be schematically illustrated as follows:

Furthermore, it is known, that solvent molecules, in particular ethers such as diethylether or THF, which are commonly used for reactions with Grignard reagents, can add to the magnesium of the Grignard reagent thereby forming etherates. Hence, formula (XI) encompasses not only the structures as depicted, but also the structures resulting from the Schleck equilibrium as well as the respective solvent adducts.

For general information regarding structures of Grignard reagents, see also Milton Orchin, Journal of Chemical Education, Volume 66, Number 7, 1999, pp 586 to 588.

The reaction of the Grignard compound of formula (XI) and manganese lithium complex of formula (XII) is preferably conducted under a protective atmosphere, preferably nitrogen or argon atmosphere. Preferably, the reaction is carried out in the presence of an aprotic solvent, preferably selected from tetrahydrofuran, methyltetrahydrofuran, in particular 2 -methyltetrahydrofuran, diethylether, cyclopentyl methyl ether, /c/7-butyl methyl ether, toluene, and mixtures thereof, most preferably selected from diethyl ether, tetrahydrofuran, toluene and mixtures thereof. Preferably, any solvent present is dried before use.

The reaction is preferably conducted at a temperature of from -10 to 30 °C, more preferred -5°C to 5 °C, and a pressure of from 0.5 to 2 bar.

Preferably, the Grignard compound of formula (XI) and the manganese lithium complex of formula (XII) are reacted in a molar ratio of 1 : 0.8 to 1 : 1.5, more preferred 1 : 0.9 to 1 : 1.4, more preferred about 1 : 1 to 1 : 1.3, most preferred 1 : 1 to 1 : 1.2.

The Grignard reagent of formula (XI) is preferably used as solution in an aprotic solvent, in particular as solution in diethyl ether, tetrahydrofuran, toluene or a mixture thereof, particularly preferred as a 0.2 to 1.0 molar solution in diethyl ether or tetrahydrofuran.

The reaction mixture resulting from the reaction of the Grignard compound of formula (XI) and the manganese lithium complex of formula (XII) can be worked-up by procedures generally known in the art, e.g. by evaporation of any organic solvent, preferably under reduced pressure. If desired, the resulting manganese compounds of formula (VIII) may be further purified by known techniques, for example crystallisation. However, preferably the resulting reaction mixture comprising the manganese compound of formula (VIII) is directly used in the preparation of a compound of formula (VII). The reaction time of each of the steps of the processes outlined above varies depending on the scale of the reaction and the reaction temperature, but is generally between a few, e.g. 5, minutes and 48 hours.

The invention further relates to novel compounds of formulae (IV) and (V), which are particularly useful in the process according to the invention and form part of the invention.

Accordingly, a further subject of this invention is a compound of formula (IV)

wherein R¹ and R² are defined as in formula (I).

Another subject of this invention is a compound of formula (V)

wherein R¹ and R² are defined as in formula (I).

The preferred, more preferred and most preferred definitions of R¹ and R² given above for formula (I) apply mutatis mutandis for compounds of formula (IV) as well as formula (V).

The invention is illustrated by the examples below. However, the invention is not limited to the examples.

Examples

Example 1:

Synthesis of 5-cyano-lH-imidazole-4-carboxamide (11-01)

lH-imidazole-4,5-dicarbonitrile (100.0 g, 0.84 mol, 1 equivalent (in the following abbreviated as equiv)) was dissolved in lN aqueous NaOH (2.11 L, 2.01 mol, 2.4 equiv) and the resulting reaction mixture was stirred at 40 °C for 8 h. Afterwards, it was cooled to 5 °C and concentrated HC1 was added adjusting the pH to 6. The forming precipitate was filtered, washed with water (3 x 350 mL) and dried at 50 °C under vacuo. The desired compound (11-01) was obtained as a white solid in 92% yield with 92% purity (114.7 g, 0.77 mol).

Example 2:

Synthesis of l-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]-5-cyano-imidazole-4-carboxamide (IV-01)

5-cyano-lH-imidazole-4-carboxamide (11-01, 35.0 g, 257.1 mmol, 1 equiv) was dissolved in dry acetonitrile (700 mL). K₂CO₃ (44.9 g, 321.4 mmol, 1.25 equiv) and 2-bromo-l-(l-chlorocyclopropyl)- ethanone (65.6 g, 308.6 mmol, 1.2 equiv) were added and the resulting reaction mixture was stirred for 16 h at room temperature (23 °C, also referred to as rt or RT). Afterwards, the solvent was removed in vacuo, water (600 mL) was added and the resulting suspension was stirred for 1 h at room temperature. The solid was filtered, washed with water (3 x 250 mL) and dried. The desired compound (IV-01) was obtained as an off- white solid in 68% yield with 90% purity (48.0 g, 171.1 mol).

The compounds of formula (IV) listed in the following Table 1 have been prepared analogously to example 2 at the given reaction temperature. Resulting yields and purities are given in this table. This shows that compounds of formula (IV) can be obtained in good to very good yield and purity by the process according to the invention.

Table 1 :

Example 3:

Alternative synthesis of l-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]-5-cyano-imidazole-4-carboxamide (IV-

01)

2-chloro-l-(l-chlorocyclopropyl)ethanone (33.0 g, 203.0 mmol, 1.2 equiv) and NaBr (25.3 g, 243.6 mmol, 1.45 equiv) were suspended in dry acetonitrile (300 mL) and stirred for 5 h under reflux. Afterwards, the reaction mixture was cooled to room temperature, 5-cyano-lH-imidazole-4-carboxamide (11-01, 25.0 g, 169.2 mmol, 1 equiv) and K2CO3 (29.5 g, 211.5 mmol, 1.25 equiv) were added and the resulting reaction mixture was stirred for 16 h at room temperature. Afterwards, the solvent was removed in vacuo, water (400 mL) was added and the resulting suspension was stirred for 1 h at room temperature. The solid was filtered, washed with water (3 x 150 mL) and dried. The desired compound (1V-01) was obtained as an off- white solid in 68% yield with 78% purity (37.4 g, 1 14.9 mol). Example 4:

Synthesis of l-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]-5-cyano-imidazole-4-carboxylic acid (V-01)

l-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]-5-cyano-imidazole-4-carboxamide (IV-01, 20.0 g, 70.9 mmol, 1 equiv) was dissolved in 40% aqueous H₂SO₄ (377 mL) and the resulting mixture was stirred at 90 °C for 3 h. Afterwards, the reaction mixture was poured into ice water (300 mL) and stirred at 5 °C for 15 min.

The forming precipitate was filtered, washed with water (3 x 30 mL) and recrystallized from 40 mL MTBE (/c/7-butyl methyl ether). The desired compound (V-01) was obtained as an off-white solid in 85% yield with 92% purity (16.6 g, 60.2 mol).

The compounds of formula (V) listed in the following Table 2 have been prepared analogously to example 4 at the given reaction temperature and time. Resulting yields and purities are given in this table. This shows that compounds of formula (V) can be obtained in good to very good yield and excellent purity by the process according to the invention.

Table 2:

Example 5:

Synthesis of 3-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]imidazole-4-carbonitrile (T01)

l-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]-5-cyano-imidazole-4-carboxylic acid (V-01, 500 mg, 1.81 mmol, 1 equiv) was dissolved in 1.65 mL dry AC₂O (acetic anhydride) and stirred at 120 °C for 2 h. After cooling to room temperature, MTBE (3 mL) was added, the resulting mixture stirred for 15 min at room temperature, filtered and the filtrate concentrated in vacuo. The remaining oil was dissolved in toluene (10 mL) and the reaction mixture was again concentrated in vacuo. The desired compound (TOl) was obtained as brown oil in 87% yield with 86% purity (385 mg, 1.58 mmol).

The compounds of formula (I) listed in the following Table 3 have been prepared analogously to example 5. Resulting yields and purities are given in this table. This shows that compounds of formula (I) can be obtained in good to very good yield and purity by the process according to the invention.

Table 3:

Example 6:

Synthesis of 3-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]imidazole-4-carbonitrile (TOl) with alternative workup to enhance purity

l-[2-(l-chlorocyclopropyl)-2-oxo-ethyl]-5-cyano-imidazole-4-carboxylic acid (V-01, 15.0 g, 56.0 mmol, 1 equiv) was dissolved in dry AC₂O (42 mL) and stirred at 120 °C for 2 h. Afterwards, the reaction mixture was concentrated in vacuo, the remaining oil dissolved in MTBE (100 mL), filtered and the solvent partly removed in vacuo (ca. 50 mL). A solution of oxalic acid (5.9 g, 64.3 mmol, 1.15 equiv) in MTBE (30 mL) was added dropwise at room temperature and the resulting mixture was stirred for 15 min. The forming precipitate was filtered and washed with MTBE (3 x 10 mL). The obtained solid was suspended in MTBE (100 mL), saturated aqueous NaHC0₃ (130 mL) was added and the resulting mixture was stirred for 1.5 h at room temperature. The phases were separated, the aqueous phase was extracted with MTBE (50 mL) and the combined organic phases concentrated in vacuo. The desired compound (TOl) was obtained as a light brown solid in 85% yield with 92% purity (10.5 g, 46.1 mmol). The compounds of formula (I) listed in the following Table 4 have been prepared analogously to example 6. Resulting yields and purities are given in this table. This shows that compounds of formula (I) can be obtained in good to very good yield and excellent purity by the process according to the invention.

(I-H)

Table 4:

Claims

1. Process for preparing a compound of formula (I)

wherein

R¹ represents hydrogen, Ci-Cs-alkyl, Ci-Cs-haloalkyl, C₂-Cs-alkenyl, C₂-Cs-haloalkenyl, C₂-C₈- alkynyl, C₂-C₈-haloalkynyl, phenyl-C₂-C₈-alkynyl, [tri(Ci-C₈-alkyl)silyl]phenyl-C₂-C₈- alkynyl, C₃-C₇-cycloalkyl, bicycloalkyl, C₃-C₇-cycloalkyl-Ci-C₄-alkyl, C₃-C₇-cycloalkyl-C₃- C₇-cycloalkyl, C₃-C₇-cycloalkenyl, tri(Ci-C₈-alkyl)silyl-Ci-C₄-alkyl, tri(Ci-C₈-alkyl)silyl-C₃- C₇-cycloalkyl, or C₆-Ci₄-aryl, wherein the phenyl-C₂-C₈-alkynyl, [tri(Ci-C₈- alkyl)silyl]phenyl-C₂-C₈-alkynyl, C₃-C₇-cycloalkyl, bicycloalkyl, C₃-C₇-cycloalkyl-Ci-C₄- alkyl, C₃-C₇-cycloalkyl-C₃-C₇-cycloalkyl, C₃-C₇-cycloalkenyl, tri(Ci-C₈-alkyl)silyl-Ci-C₄- alkyl, tri(Ci-C₈-alkyl)silyl-C₃-C₇-cycloalkyl, and C₆-Ci₄-aryl is non-substituted or substituted by one or more group(s) selected from halogen, cyano, Ci-C₄-alkyl, Ci-C₄-haloalkyl, C₁-C₄- alkoxy, Ci-C₄-haloalkoxy, Ci-C₄-alkylthio and Ci-C₄-haloalkylthio; and R² represents hydrogen, Ci-CValkyl, or C₆-Ci₄-aryl; characterized in that an imidazole of formula (II)

wherein

R² is defined as in formula (I); is reacted in a first step A) with a ketone of formula (III), o

R 1

R

(PI), wherein

R³ represents chlorine, bromine, iodine, Ci-Cs-alkylsulfonate, or C₆-Ci₄-arylsulfonate, wherein the C₆-Ci₄-arylsulfonate is non-substituted or substituted by one or more group(s) selected from halogen, Ci-C₄-alkyl, and Ci-C₄-haloalkyl; and R¹ is defined as in formula (I), to yield a compound of formula (IV),

wherein

R¹ and R² are defined as in formula (I), and in a further step B) the carbamoyl group is cleaved from the compound of formula (IV).

2. Process according to claim 1, wherein R¹ represents Ci-Cs-alkyl, optionally halogen-, cyano-, Ci- C₄-alkyl-, Ci-C₄-haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or C₁-C₄- haloalkylthio-substituted C₃-C₇-cycloalkyl or optionally halogen-, cyano-, Ci-C₄-alkyl-, C₁-C₄- haloalkyl-, Ci-C₄-alkoxy-, Ci-C₄-haloalkoxy-, Ci-C₄-alkylthio- or Ci-C₄-haloalkylthio-substituted C₆-Ci₄-aryl.

3. Process according to at least one of claims 1 and 2, wherein R² represents hydrogen.

4. Process according to at least one of claims 1 to 3, wherein R³ represents bromine.

5. Process according to at least one of claims 1 to 4, wherein the imidazole of formula (II) and the ketone of formula (III) are reacted in a molar ratio of 1 : 0.5 to 1 : 5.

6. Process according to at least one of claims 1 to 5, wherein step A) is performed in the presence of a solvent selected from acetonitrile, acetone, diethyl ether, cyclopentyl methyl ether, /c/7-butyl methyl ether, tetrahydrofuran, methyltetrahydrofuran, toluene, V-methyl-2-pyrrolidone, dimethylformamide and mixtures thereof.

7. Process according to at least one of claims 1 to 6, wherein step A) is performed in the presence of a base.

8. Process according to at least one of claims 1 to 7, wherein the cleavage of the carbamoyl group from the compound of formula (IV) in step B) is performed by treating the compound of formula (IV) in a first step Bl) with an acid selected from hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, trifluoromethanesulfonic acid, 4- methylbenzenesulfonic acid and mixtures thereof, to yield a carboxylic acid of formula (V),

wherein R¹ and R² are defined as in formula (1), and heating in a further step B2) the carboxylic acid of formula (V) in the presence of an organic solvent having a boiling point at 1 bar of from 90 °C to 300 °C or mixtures thereof, to a temperature of from 50 °C to 250 °C.

9. Process according to claim 8, wherein the acid used in step Bl) is sulfuric acid.

10. Process according to at least one of claims 8 to 9, wherein the acid used in step Bl) is present as aqueous solution.

11. Process according to at least one of claims 8 to 10, wherein the organic solvent used in step B2) is selected from nitrobenzene, dimethylformamide, /V,/V-dimcthylacctamidc, dimethyl sulfoxide, propylene carbonate, acetic anhydride and mixtures thereof.

12. Process according to at least one of claims 1 to 1 1, wherein the imidazole of formula (11) is prepared by reacting a compound of formula (VI)

(VI), wherein

R² is defined as in formula (I), with an aqueous alkali metal hydroxide solution, preferably aqueous sodium hydroxide.

13. Process according to at least one of claims 1 to 12, wherein the compound of formula (I) is further reacted to a compound of formula (VII)

wherein

R¹ is defined as in any one of claims 1 to 2;

R⁴ represents hydrogen or Ci-Cs-alkyl;

R⁵ represents hydrogen or Ci-Cs-alkyl; or R⁴ and R⁵ form together with the carbon atom to which they are attached a C₃-C₇-cycloalkyl, wherein the C₃-C₇-cycloalkyl ring is non-substituted or substituted by one or more C₁-C₄- alkyl group(s); and

Q represents a 6-membered aromatic cycle of formula (Q-I)

wherein

U¹ represents CX¹ or N;

U² represents CX² or N;

U³ represents CX³ or N;

U⁴ represents CX⁴ or N;

U⁵ represents CX⁵ or N; wherein X¹, X², X³, X⁴, and X⁵ independently from each other represent hydrogen, halogen, nitro, cyano, sulfanyl, pentafluoro^⁶-sulfanyl, Ci-Cs-alkyl, Ci-Cs-haloalkyl having 1 to 5 halogen atoms, C₃-Cs-cycloalkyl, C₃-C₇-halocycloalkyl having 1 to 5 halogen atoms, Ci-C₈- haloalkyl-C₃-C₇-cycloalkyl, C₃-C₇-cycloalkenyl, C₂-Cs-alkenyl, C₂-Cs-alkynyl, C₆-C₁₂- bicycloalkyl, C₃-C₈-cycloalkyl-C₂-Cs-alkenyl, C₃-Cs-cycloalkyl-C₂-C₈-alkynyl, Ci-Cs-alkoxy, Ci-Cs-haloalkoxy having 1 to 5 halogen atoms, Ci-Cs-alkoxycarbonyl, Ci-C₈- haloalkoxycarbonyl, Ci-Cs-alkylsulfenyl, C₂-Cs-alkenyloxy, C₃-C₈-alkynyloxy, C₃-C₆- cycloalkoxy, Ci-Cs-alkylsulfinyl, Ci-Cs-alkylsulfonyl, tri(Ci-C8-alkyl)-silyloxy, tri(Ci-C₈- alky 1) -sily 1, tri(Ci-C₈-alkyl)-silyl-C₂-C₈-alkynyl, tri(Ci-C₈-alkyl)-silyl-C₂-C₈-alkynyloxy, aryl, aryloxy, arylsulfenyl, heteroaryl, heteroaryloxy, wherein the aryl, aryloxy, arylsulfenyl, heteroaryl, heteroaryloxy is non-substituted or substituted by one or more group(s) selected from halogen, cyanosulfanyl, pentafluoro-l⁶- sulfanyl, Ci-Cs-alkyl, Ci-Cs-haloalkyl, Ci-Cs-cyanoalkyl, Ci-Cs-alkyloxy, Ci-C₈- haloalkyloxy, tri(Ci-C₈-alkyl)silyl, tri(Ci-C₈-alkyl)silyl-Ci-C₈-alkyl, C₃-C₇-cycloalkyl, C₃-C₇- halocycloalkyl, C₃-C₇-cycloalkenyl, C₃-C₇-halocycloalkenyl, C₄-Cio-cycloalkylatkyl, C₄-C₁₀- halocycloalkylalkyl, Ce-Cn-cycloalkylcycloalkyl, Ci-C₈-alkyl-C₃-C₇-cycloalkyl, Ci-Cs- alkoxy-C₃-C₇-cycloalkyl, tri(Ci-C₈-alkyl)silyl-C₃-C₇-cycloalkyl, C₂-Cs-alkenyl, C₂-C₈- alkynyl, C₂-Cs-alkenyloxy, C₂-Cs-haloalkenyloxy, C₃-Cs-alkynyloxy, C₃-C₈-haloalkynyloxy, Ci-C₈-cyanoalkoxy, C₄-C₈-cycloalkylalkoxy, C₃-C₆-cycloalkoxy, Ci-Cs-atkylsulfanyl, Ci-Cs- haloalkylsulfanyl, Ci-Cs-alkylsulfinyl, Ci-Cs-haloalkylsulfinyl, Ci-Cs-alkylsulfonyl, Ci-C₈- haloalkylsulfonyl, Ci-Cs-alkylsulfonyloxy, Ci-Cs-haloalkylsulfonyloxy, Ci-Cs-alkoxyalkyl, Ci-C₈-alkylthioalkyl, Ci-Cs-alkoxyalkoxyalkyl, Ci-Cs-haloalkoxyalkyl, benzyl, phenyl, 5- membered heteroaryl, 6-membered heteroaryl, 6-membered heteroaryloxy, benzyloxy, phenyloxy, benzylsulfanyl, and phenylsulfanyl, wherein the benzyl, phenyl, 5-membered heteroaryl, 6-membered heteroaryl, 6-membered heteroaryloxy, benzyloxy, phenyloxy, benzylsulfanyl and phenylsulfanyl is non-substituted or substituted by one or more group(s) selected from halogen, CN, nitro, Ci-Cs-alkyl, C₁-C₄- haloalkyl, Ci-C₄-alkoxy, Ci-C₄-haloalkoxy and pentafluoro-l⁶-sulfanyl; and wherein at most two of U¹, U², U³, U⁴ and U⁵ represent N; or

U¹ and U² or U² and U³ or U³ and U⁴ form together an additional saturated or unsaturated 4 to 6-membered halogen- or Ci-Cs-alkyl-substituted or non-substituted ring; characterized in that the compound of formula (I) is reacted with a manganese compound of formula (VIII),

R‘ 4 FT l^Q 77 MnY_m- z¹ M¹X„ z² LiZ

(VIII),

wherein each X, Y and Z represents independently from each other halogen; M¹ represents Mg or Zn; n is 1 or 2; m is 0 or 1 ; n+m is 2;

0 < z¹ < 10;

0 < z² < 10; and

R⁴, R⁵ and Q are defined as in formula (VII).

14. Compound of formula (IV)

wherein

R¹ and R² are defined as in formula (I).

15. Compound of formula (V)

wherein

R¹ and R² are defined as in formula (I).