Deuterio- and 3-Methylthio-Pyridine

Scale 0.10 molar for the deuteration 0.05 molar for the thiomethylation. Apparatus Chap. I, Fig. 1,11 for the deuteration, 500 ml for the methylthiolation. Introduction 

At very low temperatures 3-bromopyridine and butyllithium react cleanly, and 3-(methylthio)pyridine can be obtained in almost quantitative yield after addition of dimethyl disulfide. To minimise the danger of side-reactions (e.g. addition of BuLi across the azomethine double bond, removal of a proton vicinal to bromine) a low temperature is maintained during the halogen-metal exchange reaction. The reversed-order addition is applied to introduce deuterium, since the normal way of addition may give rise in principle to scrambling of D or introduction of more than one D e.g.  

The possibility of such undesired processes is considerable if the medium is strongly polar (e.g. if HMPT is present as a co-solvent) and/or the neutral compound has other protons which are easily abstractable. We prefer to use CH3OD rather than the cheaper D20 because CH3OD is completely soluble in the organic solvent, D20 dissolves incompletely and the undissolved D20 may solidify at the temperatures normally applied in quenching reactions so that it does not react or reacts incompletely. 

Addition of undiluted 3-bromopyridine may give rise to the formation of a brown precipitate and yields of the products are considerably lower. 

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