Nitriles from keto oximes

Fluoride ion catalyzed 1,3-dipolar cycloaddition of bromo nitrile oxide, obtained in situ from dibromoformaldehyde oxime 184, to nonactivated alkynes provides a new approach to the synthesis of neuroactive isoxazoles. However, the regioselectivity of cycloaddition in this case is not high—products 185 and 186 are obtained in a 1 1 to 1 1.4 ratio (equation 80). Cycloaddition reaction of hydroximoyl chlorides and acetylene was snc-cessfully carried out also in the presence of NaHCOs as a base. For instance, a-keto oximes 187 were reacted with acetylene and NaHCOs to give isoxazoles 188 in good yields (equation 81). 

Nitrile oxide 75, generated in situ from oxime 74, gives intramolecular 1,3-dipolar cycloaddition affording a mixture of inseparable oxocane 76 and oxonane 77 in a ratio of 1 1.4 (Scheme 11). Hydrogenation of these isoxazolines with Raney nickel leads to keto alcohols 78 and 79, which can be separated by chromatography <2006SL1205>. 

This reaction was initially reported by Granacher in 1922. It is the preparation of thionic acid by the treatment of Aldol Condensation product from an aldehyde and rhodanine with a base (e.g., NaOH). Therefore, this reaction is known as the Granacher synthesis or Granacher reaction." The prepared thionic acid in this reaction can be further converted into a variety of derivatives under different conditions. For example, it can be transformed into a-thiol acid under a basic sodium amalgam reduction, whereas aliphatic acid is formed under an acidic zinc amalgam reduction. In addition, when the thionic acid is treated with ammonia, a-keto acid is generated, and the thionic acid can be converted into af-carboxyl oxime in reaction with hydroxylamine, from which either cy-amino acid or aliphatic nitrile forms via the treatment of sodium amalgam reduction or acetic anhydride, respectively. 

Spenser and Ahmad (81, 92) found that disproportionation of N-hydroxyamino acids (27) occurs in aqueous solution. The keto acid oxime (31) decompose further to give the corresponding nitrile (33) (93) (Scheme 6). The above results are questionable as Steiger (94) and Moller et al. (95) obtained amino acids and the corresponding aldoximes (36) from aromatic N-hydroxyamino acids (34) and (35) (Scheme 7). 

Arylacetonitriles also can be prepared from the a-keto acids obtained from azlactones. The a-keto acids are isolated from the hydrolysis mixture and converted into the oximes, from which the nitriles are ob-... 

The very closely-related homoaerothionin was found in smaller quantity in both V. aerophoba and V. thiona. Its structure (8) was established by analogy with that of aerothionin 80). A full account of the work on both aerothionin and homoaerothionin, which includes discussions of the mass spectra of the parent compounds and their derivatives, has been published 143). The structure of aerothionin has now been confirmed by X-ray analysis, which also revealed the relative stereochemistry (O —H and O —N trans) 62a). The spiro systems in (7) and (8) could arise in various ways including nucleophilic attack by an oxime function on an arene oxide (15). Following suggestions that nitriles may be derived in vivo from a-aminoacids by way of a-keto- and a-oximinoacids 174), we... 

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