5,6-disubstituted-3-pyridylmethyl ammonium halide compounds useful for the preparation of 5-(substituted methyl)-2,3-pyridinedicarboxylic acids

Claim 1

A method for the preparation of a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula ##STR30## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; X is Cl, Br, I or R 3 SO 3 ; R 3 is C 1 -C 4 alkyl or phenyl optionally substituted with one to three C 1 -C 4 alkoxy groups, C 1 -C 4 alkyl groups, nitro groups, cyano groups or halogen atoms; Y and Y 1 are each independently OR 4 , NR 4 R 5 , or when taken together YY 1 is --O--, --S-- or --NR 6 --; R 4 and R 5 are each independently hydrogen, C 1 -C 4 alkyl optionally substituted with C 1 -C 4 alkoxy or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms; R 6 is hydrogen or C 1 -C 4 alkyl; Q is ##STR31## R, R 1 and R 2 are each independently C 1 -C 4 alkyl, and when taken together, R and R 1 may form a 5- or 6-membered ring in which RR 1 is represented by the structure: --(CH 2 ) n --, optionally interrupted by O, S or NR 10 , where n is an integer of 3,4 or 5, provided R 2 is C 1 -C 4 alkyl; Z 2 is O, S or NR 10 ; R 10 is C 1 -C 4 alkyl; and R 11 and R 12 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, and when taken together, R 11 and R 12 may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR 10 and optionally substituted with one to three halogen atoms, C 1 -C 4 alkyl groups or C 1 -C 4 alkoxy groups; which comprises reacting a 5-methyl-2,3-pyridinedicarboxylic acid derivative compound having the structural formula ##STR32## wherein Z, Z 1 , Y and Y 1 are as described above with a halogenating agent in the presence of a first solvent, optionally in the presence of a radical initiator to form a first mixture containing compounds having the structural formulas ##STR33## wherein, Z, Z 1 , Y and Y 1 are as described above and X is Cl or Br, reacting said first mixture with at least 1.0 molar equivalent of a C 1 -C 4 trialkylamine, a 5 to 6 membered saturated or 5 to 14 membered unsaturated heterocyclic amine, optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms in the presence of a second solvent to form said 5,6-disubstituted-3-pyridylmethyl ammonium halide compound.

Claim 2

A method for the preparation of a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula ##STR30## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; X is Cl, Br, I or R 3 SO 3 ; R 3 is C 1 -C 4 alkyl or phenyl optionally substituted with one to three C 1 -C 4 alkoxy groups, C 1 -C 4 alkyl groups, nitro groups, cyano groups or halogen atoms; Y and Y 1 are each independently OR 4 , NR 4 R 5 , or when taken together YY 1 is --O--, --S-- or --NR 6 --; R 4 and R 5 are each independently hydrogen, C 1 -C 4 alkyl optionally substituted with C 1 -C 4 alkoxy or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms; R 6 is hydrogen or C 1 -C 4 alkyl; Q is ##STR31## R, R 1 and R 2 are each independently C 1 -C 4 alkyl, and when taken together, R and R 1 may form a 5- or 6-membered ring in which RR 1 is represented by the structure: --(CH 2 ) n --, optionally interrupted by O, S or NR 10 , where n is an integer of 3,4 or 5, provided R 2 is C 1 -C 4 alkyl; Z 2 is O, S or NR 10 ; R 10 is C 1 -C 4 alkyl; and R 11 and R 12 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, and when taken together, R 11 and R 12 may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR 10 and optionally substituted with one to three halogen atoms, C 1 -C 4 alkyl groups or C 1 -C 4 alkoxy groups; which comprises reacting a 5-methyl-2,3-pyridinedicarboxylic acid derivative compound having the structural formula ##STR32## wherein Z, Z 1 , Y and Y 1 are as described above with a halogenating agent in the presence of a first solvent, optionally in the presence of a radical initiator to form a first mixture containing compounds having the structural formulas ##STR33## wherein, Z, Z 1 , Y and Y 1 are as described above and X is Cl or Br, reacting said first mixture with at least 1.0 molar equivalent of a C 1 -C 4 trialkylamine, a 5 to 6 membered saturated or 5 to 14 membered unsaturated heterocyclic amine, optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms in the presence of a second solvent to form said 5,6-disubstituted-3-pyridylmethyl ammonium halide compound.

Claim 10

A method for the preparation of a 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound having the structural formula ##STR35## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; A is O or S; and R 7 is C 1 -C 4 alkyl optionally substituted with phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms which comprises reacting a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula ##STR36## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; X is Cl, Br, I or R 3 SO 3 ; R 3 is C 1 -C 4 alkyl or phenyl optionally substituted with one to three C 1 -C 4 alkoxy groups, C 1 -C 4 alkyl groups, nitro groups, cyano groups or halogen atoms; Y and Y 1 are each independently OR 4 NR 4 R 5 , or when taken together YY 1 is --O--, --S-- or --NR 6 --; R 4 and R 5 are each independently hydrogen, C 1 -C 4 alkyl optionally substituted with C 1 -C 4 alkoxy or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms; R 6 is hydrogen or C 1 -C 4 alkyl; Q is ##STR37## R, R 1 and R 2 are each independently C 1 -C 4 alkyl, and when taken together, R and R 1 may form a 5- or 6-membered ring in which RR 1 is represented by the structure: --(CH 2 ) n --, optionally interrupted by O, S or NR 10 , where n is an integer of 3,4 or 5, provided R 2 is C 1 -C 4 alkyl; Z 2 is O, S or NR 10 ; R 10 is C 1 -C 4 alkyl; and R 11 and R 12 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, and when taken together, R 11 and R 12 may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR 10 and optionally substituted with one to three halogen atoms, C 1 -C 4 alkyl groups or C 1 -C 4 alkoxy groups; with at least 0.1 molar equivalent of an alkoxide or alkylsulfide compound having the structural formula R.sub.7 A.sup.- M.sup.+ wherein R 7 and A are as described above and M is an alkali metal in the presence of an organic solvent to form a first mixture, further reacting said first mixture with at least 2.0 molar equivalents of an aqueous base to form a second mixture and adjusting the pH of said second mixture to a value below 2.5 with an acid to form said 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound.

Claim 11

A method for the preparation of a 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound having the structural formula ##STR35## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; A is O or S; and R 7 is C 1 -C 4 alkyl optionally substituted with phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms which comprises reacting a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula ##STR36## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; X is Cl, Br, I or R 3 SO 3 ; R 3 is C 1 -C 4 alkyl or phenyl optionally substituted with one to three C 1 -C 4 alkoxy groups, C 1 -C 4 alkyl groups, nitro groups, cyano groups or halogen atoms; Y and Y 1 are each independently OR 4 NR 4 R 5 , or when taken together YY 1 is --O--, --S-- or --NR 6 --; R 4 and R 5 are each independently hydrogen, C 1 -C 4 alkyl optionally substituted with C 1 -C 4 alkoxy or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms; R 6 is hydrogen or C 1 -C 4 alkyl; Q is ##STR37## R, R 1 and R 2 are each independently C 1 -C 4 alkyl, and when taken together, R and R 1 may form a 5- or 6-membered ring in which RR 1 is represented by the structure: --(CH 2 ) n --, optionally interrupted by O, S or NR 10 , where n is an integer of 3,4 or 5, provided R 2 is C 1 -C 4 alkyl; Z 2 is O, S or NR 10 ; R 10 is C 1 -C 4 alkyl; and R 11 and R 12 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, and when taken together, R 11 and R 12 may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR 10 and optionally substituted with one to three halogen atoms, C 1 -C 4 alkyl groups or C 1 -C 4 alkoxy groups; with at least 0.1 molar equivalent of an alkoxide or alkylsulfide compound having the structural formula R.sub.7 A.sup.- M.sup.+ wherein R 7 and A are as described above and M is an alkali metal in the presence of an organic solvent to form a first mixture, further reacting said first mixture with at least 2.0 molar equivalents of an aqueous base to form a second mixture and adjusting the pH of said second mixture to a value below 2.5 with an acid to form said 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound.

Claim 18

A method for the preparation of a 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound having the structural formula ##STR39## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; A is O or S; and R 7 is C 1 -C 4 alkyl optionally substituted with phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms which comprises reacting a 5-methyl-2,3-pyridinedicarboxylic acid compound having the structural formula ##STR40## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; Y and Y 1 are each independently OR 4 , NR 4 R 5 , or when taken together YY 1 is --O--, --S-- or --NR 6 --; R 4 is hydrogen, C 1 -C 4 alkyl optionally substituted with C 1 -C 4 alkoxy or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms; and R 6 is hydrogen or C 1 -C 4 alkyl with a halogenating agent in the presence of a first solvent, optionally in the presence of a radical initiator to form a first mixture containing compounds having the structural formulas ##STR41## wherein Z, Z 1 , Y and Y 1 are as described above and X is Cl or Br, reacting said first mixture with at least about 1.0 molar equivalent of a C 1 -C 4 trialkylamine, a 5 to 6 membered saturated or 5 to 14 membered unsaturated heterocyclic amine optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms in the presence of a second solvent to form a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula ##STR42## wherein Z, Z 1 , X, Y and Y 1 are as described above and Q is ##STR43## R, R 1 and R 2 are each independently C 1 -C 4 alkyl, and when taken together, R and R 1 may form a 5- or 6-membered ring in which RR 1 is represented by the structure: --(CH 2 ) n --, optionally interrupted by O, S or NR 10 , where n is an integer of 3,4 or 5, provided R 2 is C 1 -C 4 alkyl; Z 2 is O, S or NR 10 ; R 10 is C 1 -C 4 alkyl; and R 11 and R 12 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, and when taken together, R 11 and R 12 may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR 10 and optionally substituted with one to three halogen atoms, C 1 -C 4 alkyl groups or C 1 -C 4 alkoxy groups; reacting the said 5,6-disubstituted-3-pyridylmethyl ammonium halide compound with at least 1.0 molar equivalent of an alkoxide or alkylsulfide compound having the structural formula R.sub.7 A.sup.- M.sup.+ wherein R 7 and A are as described above and M is an alkali metal in the presence of an organic solvent to form a second mixture further reacting said second mixture with at least 2.0 molar equivalents of an aqueous base to form a third mixture and adjusting the pH of said third mixture to a value below said 2.5 with an acid to form said 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound.

Claim 19

A method for the preparation of a 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound having the structural formula ##STR39## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; A is O or S; and R 7 is C 1 -C 4 alkyl optionally substituted with phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups or halogen atoms which comprises reacting a 5-methyl-2,3-pyridinedicarboxylic acid compound having the structural formula ##STR40## wherein Z is hydrogen or halogen; Z 1 is hydrogen, halogen, cyano or nitro; Y and Y 1 are each independently OR 4 , NR 4 R 5 , or when taken together YY 1 is --O--, --S-- or --NR 6 --; R 4 is hydrogen, C 1 -C 4 alkyl optionally substituted with C 1 -C 4 alkoxy or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms; and R 6 is hydrogen or C 1 -C 4 alkyl with a halogenating agent in the presence of a first solvent, optionally in the presence of a radical initiator to form a first mixture containing compounds having the structural formulas ##STR41## wherein Z, Z 1 , Y and Y 1 are as described above and X is Cl or Br, reacting said first mixture with at least about 1.0 molar equivalent of a C 1 -C 4 trialkylamine, a 5 to 6 membered saturated or 5 to 14 membered unsaturated heterocyclic amine optionally substituted with one to three C 1 -C 4 alkyl groups, C 1 -C 4 alkoxy groups or halogen atoms in the presence of a second solvent to form a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula ##STR42## wherein Z, Z 1 , X, Y and Y 1 are as described above and Q is ##STR43## R, R 1 and R 2 are each independently C 1 -C 4 alkyl, and when taken together, R and R 1 may form a 5- or 6-membered ring in which RR 1 is represented by the structure: --(CH 2 ) n --, optionally interrupted by O, S or NR 10 , where n is an integer of 3,4 or 5, provided R 2 is C 1 -C 4 alkyl; Z 2 is O, S or NR 10 ; R 10 is C 1 -C 4 alkyl; and R 11 and R 12 are each independently hydrogen, halogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, and when taken together, R 11 and R 12 may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR 10 and optionally substituted with one to three halogen atoms, C 1 -C 4 alkyl groups or C 1 -C 4 alkoxy groups; reacting the said 5,6-disubstituted-3-pyridylmethyl ammonium halide compound with at least 1.0 molar equivalent of an alkoxide or alkylsulfide compound having the structural formula R.sub.7 A.sup.- M.sup.+ wherein R 7 and A are as described above and M is an alkali metal in the presence of an organic solvent to form a second mixture further reacting said second mixture with at least 2.0 molar equivalents of an aqueous base to form a third mixture and adjusting the pH of said third mixture to a value below said 2.5 with an acid to form said 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound.