Reduction of amides to amines

R4N= BnEtsN or BU4N Heterocylces 1980, 14, 1437, 1441 reduction of amides to amines reduction of nitriles to amines... 

Scheme 46 Fe-catalyzed reduction of amides to amines under either thermal or photoassisted conditions...

Scheme 47 Fe-catalyzed hydrosilane reduction of amides to amines...

Reduction of Amides to Amines Dihydro-deoxo-bisubstitution... 

O II RCNHR 1) LiAlH4 2) H20 RCH2NHR Section 19.7 Reduction of amides to amines. 

What are the alternatives There are two main ones, and both involve functional group interconversion, with the reactive amine being converted to a less reactive derivative before disconnection. The first solution is to convert the amine to an amide and then disconnect that. The reduction of amide to amine is quite reliable, so the FGI is a reasonable one. 

The reduction of amides to amines may be achieved with lithium aluminium hydride and with borane (Scheme 3.73). 

The reduction of esters to primary alcohols and the reduction of amides to amines requires two hydrides, whereas reduction of carboxylic acids to primary alcohols consumes three hydrides (Table 4.2). 

Reduction of amides to amines.2 Primary, secondary, and especially tertiary amides are reduced by diborane to the corresponding amines rapidly and almost quantitatively. The reaction is carried out at 25° in the case of tertiary amines, and at reflux for primary and secondary amines. The method is not suitable for unsaturated... 

These reagents are strong Lewis acids that cleave THF and acetals (Section 2.4). Nevertheless, they leave bromo- and chloroderivatives intact (Section 2.1). The regioselectivity of the opening of epoxides is opposite to that observed for LAH in THF (Section 2.3). Diarylcarbinols can be reduced to hydrocarbons (Section 2.4), and a,p-unsaturated carbonyl compounds to allylic alcohols (Section 3.2.9). The reduction of amides to amines is easier than with LAH (Section 3.2.8), especially in the case of a,p-ethylenic amides or of -lactams. These reagents do not reduce NO2 groups. 

An indirect method for the reduction of amides to amines by NaBHa (applicable only to tertiary amides) involves conversion into a Vilsmeier complex [(R2N=C(C1)R)+C1 ], by treatment with Phosphorus Oxychloride, followed by its reduction. In a related methodology, primary or secondary (also cyclic) amides are first converted into ethyl imidates by the action of Triethy-loxonium Tetrafluoroborate, and the latter reduced to amines with NaBHa in EtOH or, better, with NaBHa-Tliiif/V) Chloride in Et20. ... 

More detailed information about acid/base extraction can be found in any organic practical book. The details of the Cannizarro reaction are from J. C. Gilbert and S. F. Martin, Experimental Organic Chemistry, Harcourt, Fort Worth, 2002. The reduction of amides to amines comes from B. S. Furniss, A. J. Hannaford, P. W. G. Smith,... 

The mechanism of the reduction of amides to amines by LiAIH4 contains many steps. Work as a group to figure out this mechanism. H/nf The carbonyl oxygen is removed as OAIH2. 

Although the conversion of thioamides into amines by alkylation with triethyl-oxonium tetrafluoroborate has been previously reported (c/. Vol. 4, p. 172), a considerably more detailed study has now appeared, as part of a convenient, general, and selective method for the reduction of amides to amines (Scheme 19). 

Scheme 4-340. Reduction of amides to amines catalyzed by dodecacarbonyltriiron.

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