The dehydration of amides and aldoximes

Acid amide-triphenylphosphine dihalide adducts (4) have found wide application in organic synthesis. - Synthetic equivalents are adducts (5) from acid amides and triphenylphosphine/CCU, which are prepared in situ from the educts. - With these reagents the following transformations have been performed dehydration of amides or aldoximes to nitriles, preparation of isonitriles from secondary form-amides, preparation of imidoyl halides from amides or acylhydrazines and preparation of ketene imines from amides. Using polymer-supported triphenylphosphine the work-up procedure is much easier to achieve. Triphenylphosphine can be replaced by tris(dialkylamino)phosphines. - Instead of CCI4 hexa-chloroethane, hexabromoethane or l,l,2,2-tetrabromo-l,2-dichloroethane can be used " the adducts thus formed are assumed to be more effective than those from the triphenylphosphine/CCU system. 

Tnfluoroacetic anhydride is an efficient dehydrating reagent [46, 47] In the presence of pyndine, it smoothly dehydrates amides and aldoximes to the correspond ing nitriles [46] and adducts of CH-acids and 1,2,3-indantnone [47] (equation 20)... 

Nitriles also can be obtained by the dehydration of the corresponding amide or aldoxime. This is a widely used synthetic method and numerous dehydrating agents have been found to be effective ... 

Triethoxydiiodophosphorane, (C2HsO)3Pl2 (1). Mol. wt. 389.0. The reaction of triethyl phosphite with iodine in CHjCN, CH2CI2, or ether at 0° results in a complex formulated as 1. Substances of this type are intermediates in the Arbuzov reaction. The phosphorane is stable in solution for several days. In combination with 1 equiv. of triethylamine it can dehydrate amides and aldoximes to nitriles. It effects condensation of acids and amines to amides. The paper cites one example of use for... 

Acetaldoxime conversion in the temperature range 250-350°C over B2O3/AI2O3 and H-ZSM5 is presented in figures 3 (a) and (b). In each case the major product, corresponding to greater than 90% of the converted aldoxime, was acetonitrile, which arose from the dehydration of the oxime. Small amounts of the amide also formed. 

Chlorosulfonyl isocyanate, Cl-S02-N=00, is an effective dehydrating agent for the preparation of various aryl- and alkyl-nitriles from the corresponding amides and aldoximes in yields of 74-87% and 75-86%, respectively [1128],... 

Due to their synthetic utility and pharmaceutical applications, a number of synthetic routes to a,P-unsatuiated nitriles have been developed. Classical methods include dehydration of amides [15] or aldoximes [16], Wittig- [17] and Peterson-type [18, 19] olefination processes, ammoxidation of alkenes [20], and carbocyanation of alkynes [21], These approaches suffer variously from high waste generation, low yields and poor stereoselectivity. As such the transition metal-catalysed cyanation of vinyl halides is an attractive route for the synthesis of alkaiyl nitriles. Whilst several instances of such transformations have been reported in the literature, the area remains underdeveloped, particularly in comparison to analagous cyanations of aryl halides. 

Undoubtedly, the formation of carbonic acid salts from aldoximes viaintermediale nitriles and amides also takes place in the KOH/DMSO system. Evidently this is a reason explaining why the corresponding nitrile is not generated in the aforanen-tioned system from furfurol oxime [387]. Later, it has been found that the dehydration of aldoximes into nitriles can be carried out in much softer conditions, without using the autoclave (60°C-100°C, acetylene, atmospheric pressure) [7]. In no case, pyrroles and O-vinyl oximes are identified in the reaction products. 

For further dehydration, for example, of aldoximes and amides to nitriles, of alcohols to olefines, as well as the synthesis of heterocycles like oxiranes and aziridines see Section 18.5. 

Aldehyde 26 was treated with hydroxylamine hydrochloride in refluxing methanol to give a mixture of (E)- and (Z)-pyrrolotriazine 40 in 59% and 21% yield, respectively. Dehydration of aldoxime 40 with trifluoromethanesulfonic anhydride and triethylamine in dichloromethane afforded triazine 41. Conversion of the nitrile 41 to the deprotected amide 42 was accomplished in 96% yield on treatment of 41 with basic hydrogen peroxide in ethanol <2001CAR77>. 

The fact that under the same conditions acetophenone oxime does not form amides, but remains intact, also provides evidence against the classical Beckmann rearrangement. The conditions found can be employed for preparing amides from nitriles and aldoximes, especially when the latter contain fragments unstable to acids. In the absence of DMSO, benzaldoxime is dehydrated with alkali only at the boiling point (200°C). 

Nitriles from aldoxlmes. The system trifluoroacetic anhydride and pyridine, which converts primary amides to nitriles, also converts aldoximes to nitriles. The geometrical configuration of the substrate determines the ease of dehydration (E)-Aldoximes are less reactive than (Z)-aldoximes. However, high yields can also be obtained from the former substrates if the amount of pyridine is increased or if the reaction is conducted at higher temperatures (60-65°). 

Efficient methods for the synthesis of nitriles by dehydration of aldoximes and primary amides have been developed. " The reactions were performed in the presence of a Lewis acid ionic liquid, a uranium, or a copper catalyst. 

The reaction of dichlorocarbene with primary amides, amidines, thioamides, and aldoximes all yield the corresponding nitriles. N,N-Disubstituted ureas likewise yield the corresponding N,N-disubstituted amine nitrile. This reaction amounts to a dehydration in the case of primary amides, aldoximes, and N,N-disubstituted ureas the elements of hydrogen sulfide are lost from thioamides, and HCN from amidines. 

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