Supernucleophilic 4 - substituted-pyridine catalysts, and processes useful for preparing same

A process for preparing a 4-(secondary or tertiary)aminopyridine, comprising:

• reacting a 4-substituted pyridine base having a leaving group as the 4-substituent, with an activating agent of the formula:
• 15
• wherein R3 and R4, which may be the same as or may differ from one another, are each —H or a C1-C4 alkyl group, and Z is —OR7or NR5R6, wherein R5 and R6, which may be the same as or may differ from one another, and may taken together form a ring, are each —H or C1-C8 alkyl;
• and R7 is —H or C1-C8 alkyl;
• so as to form a corresponding 1,4-substituted pyridine;
• reacting said 1,4-substituted pyridine with a primary or secondary amine to substitute an amino group for the leaving group at the 4-position, and thereby form a corresponding 1-substituted-4-(secondary or tertiary)aminopyridine, wherein said amine is included in a molar ratio of at least about 2:1 relative to the 1,4-substituted pyridine and said reacting is conducted in a substitution reaction medium essentially free from strong base;
• and
• treating the 1-substituted-4-aminopyridine compound to remove the 1-substituent and thereby form a product medium including the 4-(secondary or tertiary) amino-pyridine.

A process for preparing a 4-substituted pyridine compound, which comprises:

• first reacting a 4-substituted pyridine base having a leaving group as the 4-substituent, with an α-unsaturated of the formula
• 16
• wherein R3 and R4, which may be the same as or may differ from one another, are each —H or a C1-C4 alkyl group;
• so as to form a corresponding first 1,4-substituted pyridine betaine;
• second reacting the 1,4-substituted betaine with a nucleophile to displace the leaving group and form a second 1,4-substituted-pyridine betaine;
• and
• treating the second 1,4-substituted betaine to remove the 1-substituent and form the 4-substitued pyridine compound.

A process for forming a pyridine betaine, comprising:

• reacting a 4-substituted pyridine of the formula:
• 17
• wherein L is a leaving group selected from cyano, halo, arylsulfonyl having from six to ten carbon atoms, optionally substituted with one or more alkyl groups having from one to four carbon atoms;
• arylsulfonyloxy having from six to ten carbon atoms;
• alkylsulfonyloxy having from one to eight carbon atoms;
• aryloxy having from six to ten carbon atoms;
• arylthio having from six to ten carbon atoms;
• and nitro;
• with an α,β-unsaturated acid of the formula:
• 18
• wherein R3 and R4, which may be the same as or may differ from one another, are each —H or a C1-C4 alkyl group, so as to form a 1,4-substituted pyridine betaine of the formula:
• 19
• wherein L, R3 and R4 are as defined above.

A pyridine betaine compound of the formula

• 20
• wherein:
• G is a group selected from —CN and —NR1R2, wherein R1 and R2, which may be the same or may differ from one another, are each —H or a hydrocarbon group having from one to about ten carbon atoms;
• and
• R3 and R4, which may be the same as or may differ from one another, are selected from —H and C1-C4 alkyl groups.