2,6-Lutidine

It was first isolated from the basic fraction of coal tar and from bone oil.[1]

A laboratory route involves condensation of ethyl acetoacetate, formaldehyde, and an ammonia source to give a bis(carboxy ester) of a 2,6-dimethyl-1,4-dihydropyridine, which, after hydrolysis, undergoes decarboxylation.[3]

It is produced industrially by the reaction of formaldehyde, acetone, and ammonia.[2]

2,6-Lutidine has been evaluated for use as a food additive owing to its nutty aroma when present in solution at very low concentrations.

Due to the steric effects of the two methyl groups, 2,6-lutidine is less nucleophilic than pyridine. Protonation of lutidine gives lutidinium, [(CH₃)₂C₅H₃NH]+, salts of which are sometimes used as a weak acid because the conjugate base (2,6-lutidine) is so weakly coordinating. In a similar implementation, 2,6-lutidine is thus sometimes used in organic synthesis as a sterically hindered mild base.[4] One of the most common uses for 2,6-lutidine is as a non-nucleophilic base in organic synthesis. It takes part in the formation of silyl ethers as shown in multiple studies. [5] [6]

Oxidation of 2,6-lutidine with air gives 2,6-diformylpyridine:

C₅H₃N(CH₃)₂ + 2 O₂ → C₅H₃N(CHO)₂ + 2 H₂O

The biodegradation of pyridines proceeds via multiple pathways.[7] Although pyridine is an excellent source of carbon, nitrogen, and energy for certain microorganisms, methylation significantly retards degradation of the pyridine ring. In soil, 2,6-lutidine is significantly more resistant to microbiological degradation than any of the picoline isomers or 2,4-lutidine.[8] Estimated time for complete degradation was >30 days.[9]

• 3,5-Lutidine
• 2,4-Lutidine
• 2,6-Dimethylpiperidine
• 2,4,6-Trimethylpyridine (collidine)

Like most alkylpyridines, the LD50 of 2,6-dimethylpyridine is modest, being 400 mg/kg (oral, rat).[2]