Preparation of aromatic carboxyamides by a palladium-catalyzed carbonylation reaction

A process for preparing an aromatic carboxyamide of formula I,

• wherein
• Aryl is phenyl or a 5- or 6-membered aromatic heterocycle;
• wherein the ring member atoms of the aromatic heterocycle include besides carbon atoms 1, 2, 3, or 4 heteroatoms selected from N, O, and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from O and S;
• and wherein Aryl is further unsubstituted or further substituted with additional n identical or different radicals RA;
• wherein
• n is 0,1, 2, 3, or 4;
• RA is independently selected from the group consisting of fluorine, chlorine, cyano, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy,
• —S(═O)2—CH3, —O—C≡N, —S—C≡N, —N═C═O, —N═C═S, diC1-C6-alkylamino, —C(═O)—C1-C6-alkyl, —C(═O)—O—C1-C6-alkyl, and —CH2OH;
• R1 is C1-C6-alkyl, C1-C6-alkoxy, C3-C11-cycloalkyl, C3-C8-cycloalkenyl, C2-C6-alk-enyl, C2-C6-alkynyl, C1-C6-alkoxyimino-C1-C4-alkyl, C2-C6-alkenyloxyimino-C1-C4-alkyl, C2-C6-alkynyloxyimino-C1-C4-alkyl, C1-C6-alkylamino, diC1-C6-alkylamino, —C(═O)—C1-C6-alkyl, —C(═O)—O—C1-C6-alkyl, C(═O)—N(C1-C6-alkyl)2, phenyl-C1-C4-alkyl, phenyl-C1-C4-alkenyl, phenyl-C1-C4-alkynyl, heteroaryl-C1-C4-alkyl, phenyl, naphthyl, or a 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocycle, wherein the ring member atoms of said mono- or bicyclic heterocycle include besides carbon atoms further 1, 2, 3 or 4 heteroatoms selected from N, O and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from O and S;
• and wherein the heteroaryl group in the group heteroaryl-C1-C4-alkyl is a 5- or 6-membered aromatic heterocycle, wherein the ring member atoms of the heterocyclic ring include besides carbon atoms 1, 2, 3 or 4 heteroatoms selected from N, O, and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from O and S;
• and wherein any of the above-mentioned aliphatic or cyclic groups are unsubstituted or substituted with 1, 2, 3, or up to the maximum possible number of identical or different groups R1a;
• or
• R1 and R2, together with the nitrogen atom to which they are attached, form a saturated or partially unsaturated mono- or bicyclic 3- to 10-membered heterocycle, wherein the heterocycle includes beside one nitrogen atom and one or more carbon atoms no further heteroatoms or 1, 2 or 3 further heteroatoms independently selected from N, O, and S as ring member atoms with the provision that the heterocycle cannot contain 2 contiguous atoms selected from O and S;
• and wherein the heterocycle is unsubstituted or substituted with 1, 2, 3, 4, or up to the maximum possible number of identical or different groups R1a;
• wherein
• R1a is halogen, oxo, cyano, NO2, OH, SH, NH2, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C3-C8-cycloalkyl, —NHSO2-C1-C4-alkyl, —(C═O)—C1-C4-alkyl, —C(═O)—O—C1-C4-alkyl, C1-C6-alkylsulfonyl, hydroxyC1-C4-alkyl, —C(═O)—NH2, C(═O)—NH(C1-C4-alkyl), C1-C4-alkylthio-C1-C4-alkyl, aminoC1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, diC1-C4-alkylamino-C1-C4-alkyl, aminocarbonyl-C1-C4-alkyl, or C1-C4-alkoxy-C1-C4-alkyl;
• R2 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy, C3-C11-cycloalkyl, —C(═O) H, —C(═O)—C1-C6-alkyl, —C(═O)—C3-C11-cycloalkyl, or —C(═O)—O—C1-C6-alkyl;
• and wherein any of the aliphatic or cyclic groups in R2 are unsubstituted or substituted with 1, 2, 3, or up to the maximum possible number of identical or different radicals selected from the group consisting of halogen, hydroxy, oxo, cyano, C1-C6-alkyl, C1-C6-alkoxy, and C3-C11-cycloalkyl;
• the process comprising reacting an aromatic chloride of formula II,
• Aryl-Cl II
• wherein Aryl is as defined above for compounds of formula I, with carbon monoxide and an amine compound of formula III,
• wherein R1 and R2 are as defined above for compounds of the formula I;
• and wherein the reaction is carried out in the presence of a palladium-based catalyst, a solvent, and a base;
• and wherein the process is characterized in that the base is 1,5,7-triazabi-cyclo[4.4.0]dec-5-ene.