Regiospecific Generation of 4-Metallomethylpyridines in Organic Solvents

Transformation of 2-lutidyllithium into the 4-isomer can also be achieved by adding a chelating reagent such as TMEDA or HMPT, which destabilizes 2-lutidyllithium by competitive coordination with the metal ion. Even simple warming may cause partial formation of 4-lutidyllithium. For relevant literature the reader should consult Ref. [2] of Sect. 2. 

4-Lutidine (0.11 mol, 11.8 g, dried over machine-powdered KOH and subsequently filtered) is added in one portion to a solution of 0.1 mol of LDA (Vol. 1, Chap. I) in 70 ml of THF and 66 ml of hexane, cooled at — 40 °C. The cooling bath is removed and the temperature allowed to rise. Above 0 °C suspended material is formed in the red solution. After stirring for 30 min at + 20 °C, the formation of 4-lithio-lutidine is considered complete. 4-Methylpyridine can be metallated under similar conditions. With BuLi the metallation does not proceed cleanly (see under 2). 

Treatment of 4-methylpyridine with BuLi gives rise to some addition across the C=N bond. 

The solution of 4-lutidyllithium is poured (or transferred by a syringe with a needle of 1 mm diameter) over 5 min into a vigorously stirred mixture of 0.3 mol (28.2 g) of dimethyl disulfide and 80 ml of Et20. During this addition, the temperature is kept between —30 and — 70 °C. The product, 2-methyl-4-methylthiomethylpyridine, b.p. 104°C/12 mmHg, nD(20) 1.5629 is isolated in 80% yield in the manner described in Exp. 2. 

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