Chemistry:2,6-Lutidine
2,6-Lutidine is a natural heterocyclic aromatic organic compound with the formula (CH3)2C5H3N. It is one of several dimethyl-substituted derivative of pyridine, all of which are referred to as lutidines. It is a colorless liquid with mildly basic properties and a pungent, noxious odor.
Occurrence and production
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.[2]
It is produced industrially by the reaction of formaldehyde, acetone, and ammonia.[3]
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.[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
2,6-Lutidine also finds application in the synthesis of Nifurpirinol [13411-16-0].[7]
Biodegradation
The biodegradation of pyridines proceeds via multiple pathways.[8] 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.[9] Estimated time for complete degradation was over 30 days.[10]
See also
Toxicity
Like most alkylpyridines, the LD50 of 2,6-dimethylpyridine is modest, being 400 mg/kg (oral, rat).[3]
References
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedM - ↑ Singer, Alvin; McElvain, S. M. (1934). "2,6-Dimethylpyridine". Organic Syntheses 14: 30. doi:10.15227/orgsyn.014.0030.
- ↑ 3.0 3.1 Shimizu, Shinkichi; Watanabe, Nanao; Kataoka, Toshiaki; Shoji, Takayuki; Abe, Nobuyuki; Morishita, Sinji; Ichimura, Hisao (2007). "Ullmann's Encyclopedia of Industrial Chemistry". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399.
- ↑ Prudhomme, Daniel R.; Park, Minnie; Wang, Zhiwei; Buck, Jason R.; Rizzo, Carmelo J. (2000). "Synthesis of 2′-Deoxyribonucleosides: Β-3′,5′-Di-o-benzoylthymidine". Org. Synth. 77: 162. doi:10.15227/orgsyn.077.0162.
- ↑ Corey, E. J.; Cho, H.; Rücker, C.; Hua, D. H. (1981). "Studies with trialkylsilyltriflates: new syntheses and applications". Tetrahedron Letters 22 (36): 3455–3458. doi:10.1016/s0040-4039(01)81930-4.
- ↑ Franck, Xavier; Figadère, Bruno; Cavé, André (1995). "Mild deprotection of tert-butyl and tert-amyl ethers leading either to alcohols or to trialkylsilyl ethers". Tetrahedron Letters 36 (5): 711–714. doi:10.1016/0040-4039(94)02340-H. ISSN 0040-4039.
- ↑ "Studies on Nitrofuran Derivatives. VI. : Synthesis of 2-(5-Nitro-2-furyl)vinylpyridinemethanol and 2-(5-Nitro-2-furyl)-vinylpyridinecarboxylic acid Derivatives". YAKUGAKU ZASSHI 86 (11): 1014–1021. 1966. doi:10.1248/yakushi1947.86.11_1014. https://www.jstage.jst.go.jp/article/yakushi1947/86/11/86_11_1014/_article/-char/ja/. Retrieved 21 October 2025.
- ↑ Philipp, Bodo; Hoff, Malte; Germa, Florence; Schink, Bernhard; Beimborn, Dieter; Mersch-Sundermann, Volker (2007). "Biochemical Interpretation of Quantitative Structure-Activity Relationships (QSAR) for Biodegradation of N-Heterocycles: A Complementary Approach to Predict Biodegradability". Environmental Science & Technology 41 (4): 1390–1398. doi:10.1021/es061505d. PMID 17593747. Bibcode: 2007EnST...41.1390P. https://kops.uni-konstanz.de/bitstreams/6a1d118f-e52a-478f-8f9e-d8cbd9384229/download.
- ↑ Sims, G. K.; Sommers, L. E. (1985). "Degradation of pyridine derivatives in soil". Journal of Environmental Quality 14 (4): 580–584. doi:10.2134/jeq1985.00472425001400040022x. Bibcode: 1985JEnvQ..14..580S.
- ↑ Sims, G. K.; Sommers, L. E. (1986). "Biodegradation of Pyridine Derivatives in Soil Suspensions". Environmental Toxicology and Chemistry 5 (6): 503–509. doi:10.1002/etc.5620050601. Bibcode: 1986EnvTC...5..503S.
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