In a
2-l. round-bottomed flask provided with a
reflux condenser is placed
200 ml. of dry benzene (Note
1). A mixture of
300 g. (5.08 moles) of finely divided acetamide and
200 g. (0.9 mole) of powdered phosphorus pentasulfide is prepared quickly and transferred immediately to the flask. To this is added
20 ml. of a mixture of 400 ml. (4.97 moles) of chloroacetone (Note
2) and
150 ml. of dry benzene. The exothermic reaction is started by careful heating in a
water bath. The water bath is removed, and the remainder of the
chloroacetonebenzene mixture is introduced gradually through the
reflux condenser (Note
3) and (Note
4). When all the
chloroacetone has been added and reaction is no longer apparent, the mixture is refluxed on the water bath for 30 minutes.
About 750 ml. of water is added to the mixture with shaking. After 30 minutes the mixture is poured into a
separatory funnel, and the reddish upper layer containing the
benzene with some impurities is discarded. The lower layer is made alkaline (Note
5) by the addition of 5
N sodium hydroxide or
potassium hydroxide, and the crude
thiazole, which separates as a black upper layer, is removed with
ether, and the aqueous lower layer is extracted with five
120-ml. portions of ether. The combined ethereal extracts are dried over anhydrous
sodium sulfate and filtered through glass wool. The
ether is removed by distillation from a steam bath (Note
6), and the residual oil is fractionated at atmospheric pressure; the fraction boiling at
140–150° is collected and redistilled. The yield of
2,4-dimethylthiazole boiling at
143–145° (Note
7) is
210–230 g. (
41–45% based on the
phosphorus pentasulfide).