Thionyl Chloride reactions with secondary amides

Reactions with Secondary Amides. Treatment of AT-alkyl or A -aryl secondary amides with thionyl chloride in an inert solvent such as methylene chloride results in the formation of imidoyl chlorides (eq Q)." Upon heating, the imidoyl chlorides from N-alkylamides undergo scission to generate nitriles and alkyl chlorides via the von Braun degradation (eq 10). ... 

The simplest method of nitrile preparation is the Sj 2 reaction of CN with a primary or secondary alkyl halide, as discussed in Section 20.5. Another method for preparing nitriles is by dehydration of a primary amide, RCONH2. Thionyl chloride is often used for the reaction, although other dehydrating agents such as POCI3 also work. 

Wuts and co-workers recently reported that the Vilsmeier reagent is superior to thionyl chloride for the cyclodehydration of primary and secondary p-hydroxy amides to prepare oxazolines, in particular, for oxazoline 18b, which is used in Taxol synthesis (Scheme 8.10). Some other examples are shown in Table 8.5 (Fig. 8.3). As expected, inversion of configuration at the alcohol bearing carbon atom is observed. Of the examples examined, serine afforded low yields due to the formation of dehydroalanine. The reaction is conveniently carried out in pyridine at room temperature. p-Chloro amides are also formed, which can be converted to the oxazoline with DBU, generally using the same mixture without isolation. The... 

Thionyl chloride is frequently the reagent of choice for the dehydration of higher-molecular-weight amides, since the secondary products are gaseous and the nitrile is more readily purified. Oftentimes, the higher fatty acids are converted to the nitriles in a single operation via the intermediate ammonium salts and amides. For this purpose, dry ammonia gas is passed into the molten acids at 290-300° the yields of nitriles are excellent (80-85%). A small amount of 85% phosphoric acid appreciably reduces the reaction time. Another procedure consists in passing the acid vapors mixed with ammonia over silica gel at 500°. This technique... 

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