3,5-Dimethylpyridine → 2,3,5-Trimethylpyridine

Participants

Reaction Steps

To a solution of 3,5-lutidine (42.86, 0.400 mol) in toluene (240 ml) in a three-neck flask, under N2 atmosphere, was added dropwise MeLi [0.33M in ether, 1330 ml (0.44 mol), prepared from CH3I and Li or obtained from Aldrich]. The reaction was stirred and heated at 60°-80° C. for 6 h, after which time the ether was distilled off. The remaining solution was poured into water/crushed ice (200 ml), acidified with conc. HCl and extracted with ethyl acetate (2×100 ml). The aqueous solution then was basified with aq. NaOH and extracted with CH2Cl2 (3×100 ml). The CH2Cl2 extracts were combined, washed with sat. NaCl solution (1×50 ml), dried (MgSO4) and the solvent removed in vacuo. The residue was distilled under reduced pressure to give 2,3,5-trimethylpyridine (35.24 g, 72%) as a pale oil; bp 65°-71° C./11 mmHg. A solution of 2,3,5-trimethylpyridine (36.35 g, 0.30 mol) in AcOH (120 ml) was treated with 30% H2O (45 ml) and the mixture heated at 100° C. for 3 h. An additional aliquot of 30% H2O2 (15 ml) was added and the mixture was heated for an additional 10 h at 100° C. The reaction was cooled to rt, diluted with water (100 ml) and concentrated in vacuo. The residue again was diluted with water (200 ml), neutralized with KOH pellets and extracted with CH2Cl2 (3×100 ml). The extracts were combined, washed with sat. NaCl (1×50 ml), dried (MgSO4) and the solvent removed in vacuo to give 2,3,5-trimethylpyridine-N-oxide as a pale yellow solid, (50 g, quant.); mp 41°-42° C. (hexanes, colorless needles).

Provenance & Evidence