Preparation of substituted and unsubstituted 2-carbamoyl nicotinic and 3-quinolinecarboxylic acids

Claim 1

In a process for the preparation of a 2-(4,4-disubstituted-5-oxo(or thiono)-2-imidazolin-2-yl)-nicotinic acid and 3-quinolinecarboxylic acids of the formula: ##STR16## wherein R 1 is C 1 -C 4 alkyl; R 2 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl; and when R 1 and R 2 are taken together along with the carbon to which they are attached, they may represent C 3 -C 6 cycloalkyl optionally substituted with methyl, and when R 1 and R 2 are not the same, the optical isomers thereof; W is O or S; X is hydrogen, or C 1 -C 4 alkyl, Y is hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, trifluoromethyl, trichloromethyl, difluoromethoxy, diloweralkylamino, C 1 -C 4 alkylthio, nitro, phenyl or phenoxy optionally substituted with one C 1 -C 4 alkyl, C 1 -C 4 alkoxy or halogen; Z is hydrogen, C 1 -C 4 alkyl, trifluoromethyl, trichloromethyl, phenyl or phenyl substituted with one C 1 -C 4 alkyl, C 1 -C 4 alkoxy or halogen; and when taken together, Y and Z may form a ring in which YZ are represented by the structure: --(CH 2 ) n --, where n is an integer from 3 to 5, provided that X is hydrogen; or YZ is ##STR17## where L, M, Q and R 7 are each of hydrogen, halogen, C 1 -C 4 haloalkyl, difluoromethoxy, diloweralkylamino, C 1 -C 4 alkylthio, nitro, phenyl, phenoxy or mono-substituted phenyl or phenoxy where the substituent is C 1 -C 4 alkoxy or halogen; with the proviso that only one of L, M, Q or R 7 , may represent a substituent other than hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy which comprises reacting a compound of the structure: ##STR18## wherein X, Y and Z are as described above with a 1.0 to 1.5 equivalent, of a compound of the formula: ##STR19## wherein R 1 and R 2 are as described above; R 3 is CN, ##STR20## or ##STR21## at a temperature between 5° and 45° C. under a blanket of nitrogen, to obtain 2-carbamoyl nicotinic and 3-quinolinecarboxylic acids of formula (I) having the structure; ##STR22## wherein X, Y, Z, R 1 , R 2 and R 3 are as described above; treating the thus-formed reaction product with 2 to 10 moles of aqueous or aqueous C 1 -C 4 alcoholic sodium or potassium hydroxide; and when R 3 is CN, 2 to 5 moles of 30 to 90% aqueous hydrogen peroxide per mole of formula (I) compound, at a temperature of 25° to 110° C., acidifying the thus-formed reaction mixture to a pH between 1.5 and 4 with hydrochloric acid or sulfuric acid, and isolating the product by filtration or extraction of the acidified reaction mixture with an organic solvent and separating the solvent from the formula (IV) product, the improvement comprising carrying out the reaction for preparing the formula (I) product in the presence of a minimum of 4 molar equivalents of pyridine, 4-picoline, 2-picoline, 3-picoline, mixed picolines, quinoline, or a lutidine, either alone or in the presence of a hydrocarbon co-solvent.