Phosphorus Chloride nitriles from amides

Phosphorus oxide chloride Nitriles from carboxylic acid amides s. 17,463... 

The preparation of nitriles by the removal of water from amides can be accomplished in high yields by numerous dehydrating agents including phosphorus pentoxide, phosphorus oxychloride, and thionyl chloride. A Commonly used procedure for the preparation of simple aliphatic nitriles, e.g., isobutyronitrile (86%), consists in heating an Intimate mixture of the dry, powdered amide and phosphorus pentoxide at 100-220° and distilling the product as it is formed, sometimes under diminished pressure. ... 

Aromatic nitriles are also prepared by heating amides with phosphorus pentoxide, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, and ammonium sulfamate. In addition, the action of a double salt of aluminum and sodium chlorides, NaCl- AlClj, gives excellent yields of nitriles from both aliphatic and aromatic amides. Heating an amide with phthalic anhydride causes dehydration. A novel synthesis consists in treating a mixture of an aromatic acid and p-toluene-sulfonamide with phosphorus pentachloride the yields of nitriles range from 63% to 79%. ... 

Nitriles may be prepared from amides by dehydration with phosphorus pentoxide, phosphorus oxychloride or thionyl chloride (Scheme 3.87). 

A still unresolved problem is the structure of the often used adducts from phosphorus trihalides and carboxylic acid amides, which might be described by the formulae (8) or (9). With the aid of in situ generated adducts of acid amides and PX3 amidines, isonitriles, quinazolinones, alkyl chlorides, aminomethylenediphosphonic acids, carbamoyl halides, triformylaminomethane, 1,3,4-oxadia-zoles, sulfides (from sulfoxides), nitriles (from primary nitro compounds)" and bromoqui-nolines (from methoxyquinolines)" have been prepared. 

Treatment of the Reissert compound derived from 4-chloroisoquinoline with phosphorus pentachloride yielded 4-chloro-l-cyanoisoquinoline. Similar treatment of the benzo[/]quinoline Reissert compound gave a mixture of nitrile and amide." The Reissert compound from 2-bromo-benzo[/]quinoline with thionyl chloride gives 2-bromo-3-cyanobenzo-[/]quinoline." Oxidation of a Reissert compound in the presence of 50% sodium hydroxide and a phase transfer catalyst also gives the isoquinaldonitrile. ... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Racemic 2-ethylhexanonitrile has been obtained only by the action of phosphorus pentachloride on 2-ethylhexanaldoxime 4 the levorotatory form has been prepared from the active amide by the method described.6 Other amides have been converted to nitriles by dehydration with thionyl chloride.6-6... 

Phosphorus nitrile chloride forms adduct (10) with DMF in the ratio 1 4, which is useful for the preparation of formamidines and azavinylogous formamidinium salts. It is supposed that the dehydration of primary amides to nitriles with (PNChls as well as the formation of 2-alkylbenzothiazoles from 2-(methylthio)anilides and (PNChls in the presence of triethylamine proceed via similar adducts." ... 

Several phosphorus compounds have been used for the first time as dehydrating scents on amides. Diethyl phosphorochloridate in the presence of triethyl-amine converts aliphatic and benzenoid amides to nitriles at 65° the yields vary from 30% for acetonitrile to 72% for propanenitrile [27]. Even milder conditions suffice when pyrophosphoryl chloride is used [28] this reaction enables a... 

Nitriles are prepared by a wide variety of methods [24]. Dehydration of amides has been accomplished using acidic reagents such as phosphorus pentoxide [25] or thionyl chloride [26]. Nitriles can be prepared from the corresponding amides in high yields at 0°C using phenyl chlorothionofor-mate [27]. Aldehydes can be converted to nitriles in the presence of a variety of functionality using 0-(diphenylphosphinyl)hydroxylamine (DPPH) as shown in Equation 6.16 [28]. 

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