Dehydration of primary amides

By the dehydration of primary amides with phosphorus pentoxide or with thionyl chloride, for example ... 

The dehydration of primary amides with hydrosilane catalyzed by iron carbonyl clusters, such as [Et3NH][HFe3(CO)n] and Fe2(CO)9, was achieved by Seller and coworkers in 2009 (Scheme 43) [145]. This reaction shows good functional group tolerance (e.g., such as aromatic, heteroaromatic, and aliphatic substrates). 

Scheme 44 Plausible pathway of Fe-catalyzed dehydration of primary amides to nitriles...

Many methods for the dehydration of primary amides to nitriles involve the use of strong acids and/or other reagents which are incompatible with sensitive functionality. French workers have recently described an unusual, mild, efficient (64-92%) and fairly general procedure for the RCONH2 —> RCN transformation which simply involves heating a mixture of the amide, an aldehyde and formic acid under reflux in acetonitrile for 12 hours. The following observations were made ... 

Nitriles can be prepared by the SN2 reaction of a cyanide ion with a primary alkyl halide. However, this limits the nitriles that can be synthesised to those having the following general formula RCH2CN. A more general synthesis of nitriles involves the dehydration of primary-amides with reagents such as thionyl chloride or phosphorus pentoxide ... 

Fig. Dehydration of primary amides with thionyl chloride.

Figure 7.4 illustrates the dehydration of primary amides A to nitriles B using trifluo-romethanesulfonic acid anhydride. All intermediates correspond to the ones discussed above. When the mixed anhydrides F finally release trifhioromethanesulfonic acid in two steps hy the already familiar El mechanism, the formation of the nitrile B is completed. 

They can also be prepared by SOCI2 dehydration of primary amides. 

Nitriles can be prepared by dehydration of primary amides (reaction 8) or of aldoximes (reaction 9), catalyzed by the Re trioxo compounds [ReOsX] (X = OSiMes, OReOs, OH) in azeotropic (e.g. toluene/water or mesitylene/water) reflux. Aqueous perrhenic acid (X = OH) is the most convenient catalyst in view of the moisture sensitivity of the others. The oxophilicity of the Re(VII) oxo-complexes is believed to play a determining role in the reactions, which are proposed to involve six-membered cyclic transition states formed upon preferential (9-coordination, relative to A-coordination, of the amide or oxime. ... 

The reduction of nicotinamide (31) with NBH in diglyme at 140° C gave a low yield of tetrahydropyridine (22) and the piperidine 32. Addition of ethanol as a proton source raised the yield of 22 to 42%. The dehydration of primary amides with borohydride is known to occur in moderate yield. The reduction of 2-alkylamino- and 2-arylamino-3,5-dinitropyridines (33) in water leads to the tetrahydropyridines 34 in high yields. - The... 

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." ... 

Dibutyltin oxide catalyses the dehydration of primary amides or thionoamides to nitriles under neutral conditions. The reaction can be represented as a cyclic elimination involving the 0-stannyl (or S-stannyl) isomer.56... 

RCONH2 — RCN. The dehydration of primary amides under nonacidic conditions employs Ag O, molecular sieves and EtI. 

RCONH2 —>RCN. This dehydration of primary amides is performed by heating with formic acid and (HCHO) in MeCN. Amides in which the a-position is fully substituted undergo the dehydration without any problem. 

Isocyanides can be made from treatment of formamides with tosyl chloride in pyridine, as illustrated in eq 42. Similarly, nitriles can be synthesized in moderate to good yields by dehydration of primary amides using tosyl chloride in p)Tidine or... 

TfzO and a base can effect dehydration of primary amides to nitriles. This procedure is particularly mild, with no epimer-ization observed at the stereogenic a-carbon of several substrates (eq 63). ... 

The above mechanism is similar to that proposed by Nakajima [13] for the dehydration of primary amides under Swem conditions. There is an obvious analogy between a sulfoxonium salt and chloroformate ... 

Itagaki S, KamataK, Yamaguchi K, Mizuno N (2013) Amonovacantlacunary silicotungstate as an efficient heterogeneous catalyst for dehydration of primary amides to nitriles. ChemCatChem 5 1725-1728... 

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