2,6-Lutidine

Occurrence and production

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

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.

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

Uses

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.{{cite journal|title=Synthesis of 2′-Deoxyribonucleosides: Β-3′,5′-Di-o-benzoylthymidine 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.

Oxidation of 2,6-lutidine with air gives 2,6-diformylpyridine: :C5H3N(CH3)2 + 2 O2 → C5H3N(CHO)2 + 2 H2O

2,6-Lutidine also finds application in the synthesis of Nifurpirinol [13411-16-0].

Biodegradation

The biodegradation of pyridines proceeds via multiple pathways. 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. Estimated time for complete degradation was over 30 days.

Toxicity

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

References

References

1. {{Merck11th. 5485
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5. (1995). "Mild deprotection of ''tert''-butyl and ''tert''-amyl ethers leading either to alcohols or to trialkylsilyl ethers". Tetrahedron Letters.
6. (1966). "Studies on Nitrofuran Derivatives. VI. : Synthesis of 2-(5-Nitro-2-furyl)vinylpyridinemethanol and 2-(5-Nitro-2-furyl)-vinylpyridinecarboxylic acid Derivatives". Yakugaku Zasshi.
7. (2007). "Biochemical Interpretation of Quantitative Structure-Activity Relationships (QSAR) for Biodegradation of ''N''-Heterocycles: A Complementary Approach to Predict Biodegradability". Environmental Science & Technology.
8. (1985). "Degradation of pyridine derivatives in soil". Journal of Environmental Quality.
9. (1986). "Biodegradation of Pyridine Derivatives in Soil Suspensions". Environmental Toxicology and Chemistry.