Aliphatic amidoximes

Related (diisopropoxyphosphoryl)- and (diisobutoxyphosphoryl)formonitrile oxides (114), generated in basic media from the corresponding oximes react in situ with alcohols, phenols, alkanethiols, thiophenols, aliphatic and aromatic primary amines, hydrazines and hydrazides as well as 4-aminoantipyryne to give hydroxymates, thiohydroxymates, and amidoximes, respectively. It is important to note that the addition is stereoselective and gives E-adducts with the exception of (i-Pr0)2P(0)C( N0H)0Me, which is formed as a 1 1 mixture of E and Z isomers. 

In contrast, the oxidation of oxadiazolines (method S) can be used to synthesize oxadiazoles from aromatic amidoximes and aliphatic aldehydes. 

Amidoximes readily condense with aliphatic aldehydes in aqueous solution to form 4,5-dihydro-l,2,4-oxadiazoles (oxadiazolines). 

The reaction of amides35 with amidoxime salts is especially felicitous because no solvent is needed and recovery is simple. The two components are melted together at 160-180° for 10 minutes, and water is lost at the elevated temperature. Both aliphatic and aromatic (di- and monosubstituted) amidoximes give yields in the range 60-90%. Whether an O-acyl (or an TV-acyl) intermediate (4) is formed has not been determined. 

Regioselective functionalization of the N-3 of 125 with 1,2,4-oxadiazole as amide isostere using an IL-bound 125 with chloroacetonitrile afforded N-3 substituted 126 (Scheme 48). The nitrile group of 126 was transformed into amidoxime 127 with hydroxylamine hydrochloride. Addition of aliphatic carboxylic anhydrides or aromatic carboxylic acid to 127 furnished 129 via the 0-acylamidoxime intermediate 128, after cleavage from the IL (07TL1063) (Scheme 48). 

Amidoximes from aliphatic nitro compds. CHNO2 C(NC) = NOH... 

However, the drawback of this reaction is the need of a stoichiometric PhI(OAc)2 to maintain the catalytic turnover and it needs two-electron oxidation to realize the aliphatic C-H amination. They reported that the amidoximes such as readily available A/ -alkylamidoximes could be used as a precursor of the amidinyl radical to realize this C(sp )-H amination. A redox-neutral radical pathway including a Cu(I)-Cu(II) redox catalytic cycle is proposed for this reaction [86] (Scheme 8.47). 

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