Dehydration, of amides

Nitriles are important organic intermediates for a variety of ene products. Rao tt al. reported the dehydration of amides to nitriles by passing the vapor of amides through ZSM-5 zeolites at 673 Benzamide, phenacetamide, nicotinamide and isovaleramide gave the corresponding nitriles in 90%, 85%, 89% and 85% yields, respectively. 

Dehydration of amides is often carried out in the presence of ammonia. Acetonitrile, adiponitrile, and 6-aminocaprolactam ° are formed from acetamide, adipic acid and E-aminocaprolactam over MgiPiO , phosphoric acid supported on silica, and MgHP04, respectively in high yields. o-Chloronitrile can be produced from o-chlorobenzoic acid or its amide over alumina around 623 

The dehydration of formamides leads to the formation of nitriles. This reaction can be classified as a homologation reaction, i.e., a reaction bringing about an increase in the hydrocarbon chain of an organic molecule. The transformation corresponds to dehydration to isonitrile, followed by rearrangement of the latter to nitrile. 

Ishida and Chono describe similar reactions over M0O3 or WO3 supported on silica. Thus, an n-vtderonitrile yield of 73% was obtained with a selectivity of 84% over MoOs/SiOa at 703 K. Similarly, 7V-hexylformamide, formanilide, A7-cyclohexyl-formamide, A, 7V -hexamethyleneformamide and Af-benzylformamide gave nitriles in 50 — 80% selectivity. 

Boresok, F. Solymosi, Z. G. Szabo, Proc. 3rd Int. Congr. Catalysis, Amsterdam 1964, North Holland, Amsterdtim, 1965, p.l340. 

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Cyanothiazoles can be prepared by different methods. Dehydration of amides to give nitriles has already been mentioned. The yields are good... 

Both alkyl and aryl nitriles are accessible by dehydration of amides... 

Section 20 18 Nitnles are prepared by nucleophilic substitution (8 2) of alkyl halides with cyanide ion by converting aldehydes or ketones to cyanohydrins (Table 20 6) or by dehydration of amides... 

Nitdles may be prepared by several methods (1). The first nitrile to be prepared was propionitdle, which was obtained in 1834 by distilling barium ethyl sulfate with potassium cyanide. This is a general preparation of nitriles from sulfonate salts and is referred to as the Pelou2e reaction (2). Although not commonly practiced today, dehydration of amides has been widely used to produce nitriles and was the first commercial synthesis of a nitrile. The reaction of alkyl hahdes with sodium cyanide to produce nitriles (eq. 1) also is a general reaction with wide appHcabiUty ... 

Hydrolysis of primary amides cataly2ed by acids or bases is very slow. Even more difficult is the hydrolysis of substituted amides. The dehydration of amides which produces nitriles is of great commercial value (8). Amides can also be reduced to primary and secondary amines using copper chromite catalyst (9) or metallic hydrides (10). The generally unreactive nature of amides makes them attractive for many appHcations where harsh conditions exist, such as high temperature, pressure, and physical shear. 

Eatty amines are made by dehydration of amides to nitriles at 280—330°C, followed by hydrogenation of the nitrile over nickel or cobalt catalysts ... 

Dehydration of Amides, Oximes, and Ketene Imines into Nitriles... 

Dehydration of amides.1 Primary amides are converted by this reagent into nitriles at 25° in 82-92% yield. Actually, this reaction occurs more readily than dehydration of a secondary hydroxyl group. 

Carboxylic acid derivatives are compounds that possess an acyl group (R—C=0) linked to an electronegative atom, e.g. —Cl, —CO2 R, —OR or —NH2. They can be converted to carboxylic acids via simple acidic or basic hydrolysis. The important acid derivatives are acid chlorides, acid anhydrides, esters and amides. Usually nitriles are also considered as carboxylic acid derivatives. Although nitriles are not directly carboxylic acid derivatives, they are conveniently hydrolysed to carboxylic acids by acid or base catalysts. Moreover, nitriles can be easily prepared through dehydration of amides, which are carboxylic acid derivatives. 

In addition to the procedures listed in Table 3.38, further reactions have been used to generate halides upon cleavage. In Section 3.5.2, iodolactonization is presented as a method for the preparation of iodomethyl lactones from resin-bound pentenoic or hexenoic acid derivatives. Closely related to the iodolactonization is the iodine-mediated formation of 2-(iodomethyl)tetrahydrofurans from resin-bound isoxazoli-dines (Entry 9, Table 3.38 for the mechanism, see Figure 15.5). Nitriles can also be prepared by cleavage and simultaneous dehydration of amides RCONH2 from the Rink or Sieber linkers with TFA anhydride (Entry 10, Table 3.38). 

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