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

Claim 1

A 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula wherein Z   is hydrogen or halogen; Z₁   is hydrogen, halogen, cyano or nitro; X   is Cl, Br, I or R₃SO₃; R₃   is C₁-C₄ alkyl or phenyl optionally substituted with one to three C₁-C₄ alkoxy groups, C₁-C₄ alkyl groups, nitro groups, cyano groups or halogen atoms; Y and Y₁   are each independently OR₄, NR₄R₅, or when taken together YY₁ is -O-, -S- or -NR₆-; R₄ and R₅   are each independently hydrogen, C₁-C₄ alkyl optionally substituted with C₁-C₄ alkoxy or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms; R₆   is hydrogen or C₁ - C₄ alkyl; Q   is R, R₁ and R₂   are each independently C₁-C₄ alkyl, and when taken together, R and R₁ may form a 5- or 6-membered ring in which RR₁ is represented by the structure: -(CH₂) n -, optionally interrupted by O, S or NR₁₀, where n is an integer of 3,4 or 5, provided R₂ is C₁-C₄ alkyl; Z₂   is O, S or NR₁₀; R₁₀   is C₁-C₄ alkyl; and R₁₁ and R₁₂   are each independently hydrogen, halogen, C₁-C₄ alkyl or C₁-C₄ alkoxy, and when taken together, R₁₁ and R₁₂ may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR₁₀ and optionally substituted with one to three halogen atoms, C₁-C₄ alkyl groups or C₁-C₄ alkoxy groups.

Claim 4

A method for the preparation of a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula wherein Z   is hydrogen or halogen; Z₁   is hydrogen, halogen, cyano or nitro; X   is Cl, Br, I or R₃SO₃; R₃   is C₁-C₄ alkyl or phenyl optionally substituted with one to three C₁-C₄ alkoxy groups, C₁-C₄ alkyl groups, nitro groups, cyano groups or halogen atoms; Y and Y₁   are each independently OR₄, NR₄R₅, or when taken together YY₁ is -O-, -S- or -NR₆-; R₄ and R₅   are each independently hydrogen, C₁-C₄ alkyl optionally substituted with C₁-C₄ alkoxy or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms; R₆   is hydrogen or C₁ - C₄ alkyl; Q   is R, R₁ and R₂   are each independently C₁-C₄ alkyl, and when taken together, R and R₁ may form a 5- or 6-membered ring in which RR₁ is represented by the structure: -(CH₂) n -, optionally interrupted by O, S or NR₁₀, where n is an integer of 3,4 or 5, provided R₂ is C₁-C₄ alkyl; Z₂   is O, S or NR₁₀; R₁₀   is C₁-C₄ alkyl; and R₁₁ and R₁₂   are each independently hydrogen, halogen, C₁-C₄ alkyl or C₁-C₄ alkoxy, and when taken together, R₁₁ and R₁₂ may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR₁₀ and optionally substituted with one to three halogen atoms, C₁-C₄ alkyl groups or C₁-C₄ alkoxy groups; which is characterized by reacting a 5-methyl-2,3-pyridinedicarboxylic acid derivative compound having the structural formula wherein Z, Z₁, Y and Y₁ 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 wherein Z, Z₁, Y and Y₁ are as described above and X is Cl or Br, reacting said first mixture with at least 1.0 molar equivalent of a C₁-C₄ trialkylamine, a 5 to 6 membered saturated or 5 to 14 membered unsaturated heterocyclic amine, optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms in the presence of a second solvent to form said 5,6-disubstituted-3-pyridylmethyl ammonium halide compound.

Claim 7

A method for the preparation of a 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound having the structural formula wherein Z   is hydrogen or halogen; Z₁   is hydrogen, halogen, cyano or nitro; A   is O or S; and R₇   is C₁-C₄ alkyl optionally substituted with phenyl optionally substituted with one to three C₁-C₄ alkyl groups or halogen atoms, or phenyl optionally substituted with one to three C₁-C₄ alkyl groups or halogen atoms which is characterized by reacting a 5,6-disubstituted-3-pyridylmethyl ammonium halide compound having the structural formula wherein Z   is hydrogen or halogen; Z₁   is hydrogen, halogen, cyano or nitro; X   is Cl, Br, I or R₃SO₃; R₃   is C₁-C₄ alkyl or phenyl optionally substituted with one to three C₁-C₄ alkoxy groups, C₁-C₄ alkyl groups, nitro groups, cyano groups or halogen atoms; Y and Y₁   are each independently OR₄, NR₄R₅, or when taken together YY₁ is -O-, -S- or -NR₆-; R₄ and R₅   are each independently hydrogen, C₁-C₄ alkyl optionally substituted with C₁-C₄ alkoxy or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms; R₆   is hydrogen or C₁ - C₄ alkyl; Q   is R, R₁ and R₂   are each independently C₁-C₄ alkyl, and when taken together, R and R₁ may form a 5- or 6-membered ring in which RR₁ is represented by the structure: -(CH₂) n -, optionally interrupted by O, S or NR₁₀, where n is an integer of 3,4 or 5, provided R₂ is C₁-C₄ alkyl; Z₂   is O, S or NR₁₀; R₁₀   is C₁-C₄ alkyl; and R₁₁ and R₁₂   are each independently hydrogen, halogen, C₁-C₄ alkyl or C₁-C₄ alkoxy, and when taken together, R₁₁ and R₁₂ may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR₁₀ and optionally substituted with one to three halogen atoms, C₁-C₄ alkyl groups or C₁-C₄ alkoxy groups; with at least 0.1 molar equivalent of an alkoxide or alkylsulfide compound having the structural formula R₇A⁻M⁺ wherein R₇ 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 9

A method for the preparation of a 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound having the structural formula wherein Z   is hydrogen or halogen; Z₁   is hydrogen, halogen, cyano or nitro; A   is O or S; and R₇   is C₁-C₄ alkyl optionally substituted with phenyl optionally substituted with one to three C₁-C₄ alkyl groups or halogen atoms, or phenyl optionally substituted with one to three C₁-C₄ alkyl groups or halogen atoms which is characterized by reacting a 5-methyl-2,3-pyridinedicarboxylic acid compound having the structural formula wherein Z   is hydrogen or halogen; Z₁   is hydrogen, halogen, cyano or nitro; Y and Y₁   are each independently OR₄, NR₄R₅, or when taken together YY₁ is -O-, -S- or -NR₆-; R₄   is hydrogen, C₁-C₄ alkyl optionally substituted with C₁-C₄ alkoxy or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms, or phenyl optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ alkoxy groups or halogen atoms; and R₆   is hydrogen or C₁-C₄ 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 wherein Z, Z₁, Y and Y₁ are as described above and X is Cl or Br, reacting said first mixture with at least about 1.0 molar equivalent of a C₁-C₄ trialkylamine, a 5 to 6 membered saturated or 5 to 14 membered unsaturated heterocyclic amine optionally substituted with one to three C₁-C₄ alkyl groups, C₁-C₄ 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 wherein Z, Z₁, X, Y and Y₁ are as described above and Q   is R, R₁ and R₂   are each independently C₁-C₄ alkyl, and when taken together, R and R₁ may form a 5-or 6-membered ring in which RR₁ is represented by the structure: -(CH₂) n -, optionally interrupted by O, S or NR₁₀, where n is an integer of 3,4 or 5, provided R₂ is C₁-C₄ alkyl; Z₂   is O, S or NR₁₀; R₁₀   is C₁-C₄ alkyl; and R₁₁ and R₁₂   are each independently hydrogen, halogen, C₁-C₄ alkyl or C₁-C₄ alkoxy, and when taken together, R₁₁ and R₁₂ may form a 5- or 6-membered saturated or unsaturated ring optionally interrupted by O, S, or NR₁₀ and optionally substituted with one to three halogen atoms, C₁-C₄ alkyl groups or C₁-C₄ alkoxy groups; reacting the said 5,6-disubstituded-3-pyridylmethyl ammonium halide compound with at least 1.0 molar equivalent of an alkoxide or alkylsulfide compound having the structural formula R₇A⁻M⁺ wherein R₇ 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 about 2.5 with an acid to form said 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compound.