Methods for the preparation of aryl amides

A method of preparing a compound of formula IA comprising performing the reaction represented by scheme 1A:

• wherein
• Q is phenyl or 5-6 membered heteroaryl containing 1 or 2 heteroatoms independently selected from O, N and S, wherein the phenyl and heteroaryl are optionally substituted by one or more groups independently selected from halogen, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, cyano, hydroxyl, and amino;
• and
• wherein, in addition to the foregoing, the phenyl or heteroaryl is substituted at the ortho position with respect to X by a group selected from phenyl, C1-C8-alkyl, C1-C8-alkoxy, or C3-C6-cycloalkyl, and wherein each phenyl, C1-C8-alkyl, C1-C8-alkoxy, and C3-C6-cycloalkyl is optionally substituted by one or more groups independently selected from halogen, C1-C8-alkyl, C1-C8-alkoxyl, C3-C6-cycloalkyl, C1-C8-haloalkyl, C1-C8-haloalkoxy, and C3-C6-halocycloalkyl;
• or
• when Q is phenyl it is substituted at the ortho- and meta-position with respect to X by a fused bicyclo[2.2.1]heptane or bicyclo[2.2.1]heptene ring, each optionally substituted with one or more groups independently selected from halogen, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-alkoxy, C1-C8-alkylthio, C1-C8-alkylamino, cyano, and hydroxyl, wherein any alkyl, haloalkyl, alkoxy, alkylthio, or alkylamino substituent may join with another alkyl, haloalkyl, alkoxy, alkylthio, or alkylamino substituent to form a ring;
• or the fused bicyclo[2.2.1]heptane or bicyclo[2.2.1]heptene ring is optionally substituted by ═N—N(R4b)R5b, wherein R4b and R5b are independently selected from C1-C8-alkyl;
• or the fused bicyclo[2.2.1]heptane or bicyclo[2.2.1]heptene ring is optionally substituted by ═C(R3a)R4a wherein R3a and R4a are independently selected from C1-C8 alkyl and C1-C8 haloalkyl;
• X is halogen or a sulphonate;
• P is phenyl, pyridyl, pyrrole, or pyrazole, each optionally substituted with one to three substituents independently selected from C1-C4-alkyl, C1-C4-haloalkyl and halogen;
• R is hydrogen or methyl;
• wherein the catalyst comprises copper and a ligand, wherein the ligand is an optionally substituted 1,2 diamine or an optionally substituted 1,3 diamine;
• wherein the reaction is performed in an organic polar solvent;
• comprising the steps:
• a) providing the compound of formula IIIA in liquid form,
• b) contacting the copper with the compound of formula IIIA,
• c) contacting the ligand with the compound of formula IIIA,
• wherein at least one of steps b) and c) is performed after step a);
• wherein step a) comprises heating the compound of formula IIIA.

A method of preparing a compound of formula ID comprising performing the reaction represented by scheme 1D:

• wherein Q is group V, group VI or group VIIa, group VIIb or group VIIc:
• B is a single or double bond;
• T is a single or double bond;
• R1a is phenyl optionally substituted with one to three halogen atoms, or R1a is C1-C8-alkyl, C1-C8-haloalkyl or
• R2a, R3a and R4a are each independently C1-C8 alkyl or C1-C8 haloalkyl;
• Y2 and Y3 are independently O, S, N;
• R2b and R3b are independently C1-C8-alkyl, wherein R2b and R3b are optionally joined to form a 5-8 membered ring;
• R4b and R5b are independently C1-C8-alkyl;
• R5a is hydrogen or halogen;
• X is chlorine;
• R is hydrogen;
• P is group VIII or group IX:
• wherein R1 is CF3, CHF2 or CH2F;
• wherein Rx is selected from CF3, CHF2 and CH3;
• wherein the catalyst comprises copper and a ligand;
• wherein the ligand is an optionally substituted 1,2 diamine or an optionally substituted 1,3 diamine;
• comprising the steps:
• a) providing the compound of formula IIID in liquid form,
• b) contacting the copper with the compound of formula IIID,
• c) contacting the ligand with the compound of formula IIID,
• wherein at least one of steps b) and c) is performed after step a);
• wherein step a) comprises heating the compound of formula IIID.