Process for the preparation of substituted phenyl ketones

A process for the preparation of triazole compounds of the formula (IC)

• wherein R1 is C1-C6-alkyl or C3-C8-cycloalkyl;
• and
• R2 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C8-cycloalkyl, C3-C8-cycloalkyl-C1-C6-alkyl, phenyl, phenyl-C1-C4-alkyl, phenyl-C2-C4-alkenyl or phenyl-C2-C4-alkynyl;
• wherein the aliphatic moieties of R2 are not further substituted or do carry one, two, three or up to the maximum possible number of identical or different groups
• R12a which independently are selected from:
• R12a halogen, OH, CN, nitro, C1-C4-alkoxy, C3-C8-cycloalkyl, C3-C8-halocycloalkyl and C1-C4-halogenalkoxy;
• wherein the cycloalkyl and/or phenyl moieties of R2 are not further substituted or do carry one, two, three, four, five or up to the maximum number of identical or different groups R12b which independently are selected from:
• R12b halogen, OH, CN, nitro, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-halogenalkyl, C3-C8-cycloalkyl, C3-C8-halocycloalkyl and C1-C4-halogenalkoxy;
• and
• R4 is F or Cl
• comprising the following steps:
• (i) preparing a compound of formula (II)
• by reacting a compound of the formula (III)
• with R′—Mg-Hal (IV) or Mg, and R1C(═O)Cl (V),
• wherein the Grignard reagent is added as solution in a solvent selected from tetrahydrofurane (THF), 1,4-dioxane, diethylether and 2-methyl-tetrahydrofurane,
• wherein the temperature during the reaction with (V) is kept in the range of −20° C. to 10° C.,
• wherein
• R′ is C1-C4-alkyl or C3-C6-cycloalkyl and
• Hal is halogen;
• (ii) reacting compound (II) as defined in step (i) with a phenol derivative of formula (VI)
• wherein
• R″ is hydrogen or an alkali metal kation;
• in the presence of a base if R″ is hydrogen to result in a ketone of formula (IA)
• (iii) reacting the ketone of the formula (IA) as defined in step (ii) to oxiranes (IB);
• and
• (iv) reacting the oxirane (IB) as defined in step (iii) with 1H-1,2,4-triazole in the presence of a base to obtain compounds (IC), wherein R2 is hydrogen (compounds IC-1);
• and, for obtaining compounds wherein R2 is different from hydrogen (compounds IC-2);
• (v) derivatizing the compound of formula (IC-1) as defined in step (iv) under basic conditions with R2-LG, wherein LG is a nucleophilically replaceable leaving group;
• to result in compounds (IC-2).